Revealing factors determining immunodominant responses against dominant epitopes
AbstractUpon recognition of peptide-MHC complexes by T cell receptors (TCR), the cognate T cells expand and differentiate into effector T cells to generate protective immunity. Despite the fact that any immune response generates a diverse set of TCR clones against a particular epitope, only a few clones are highly expanded in any immune response. Previous studies observed that the highest frequency clones usually control viral infections better than subdominant clones, but the reasons for this dominance among T cell clones are still unclear. Here, we used publicly available TCR amino acid sequences to study which factors d...
Source: Immunogenetics - December 6, 2019 Category: Genetics & Stem Cells Source Type: research

Differences in MHC-B diversity and KIR epitopes in two populations of wild chimpanzees
AbstractThe major histocompatibility complex (MHC) class I genes play a critical role within the immune system, both by the presentation of antigens from intracellular pathogens to immunocompetent cells and by the interaction with killer cell immunoglobulin-like receptors (KIR) on natural killer cells (NK cells). Genes of the MHC are highly diverse, and MHC variation can have effects on the immune functionality of individuals; hence, comparisons of MHC diversity among closely related phylogenetic taxa may give insight into the factors responsible for the shaping of its diversity. The four geographically separated chimpanze...
Source: Immunogenetics - December 3, 2019 Category: Genetics & Stem Cells Source Type: research

Characterization of the ferret TRB locus guided by V, D, J, and C gene expression analysis
In this study, we analyzed the published T cell receptor beta (TRB) locus and performed high-throughput sequencing (HTS) of peripheral blood of four healthy adult ferrets to identify expressed V, D, J, and C genes. The HTS data is used as a guide to manually curate the expressed V, D, J, and C genes. The ferret locus appears to be most similar to that of the dog. Like other mammalian TRB loci, the ferret TRB locus contains a library of variable genes located upstream of two D-J-C gene clusters, followed by a (in the ferret non-functional) V gene with an inverted transcriptional orientation. All TRB genes (expressed or not)...
Source: Immunogenetics - December 3, 2019 Category: Genetics & Stem Cells Source Type: research

Nomenclature report for killer-cell immunoglobulin-like receptors (KIR) in macaque species: new genes/alleles, renaming recombinant entities and IPD-NHKIR updates
This report lists the names of quality controlled and annotatedKIR genes/alleles with all the relevant references for two different macaque species: rhesus and cynomolgus macaques. Numerous recombinantKIR genes in these species necessitate a revision of some of the earlier-published nomenclature guidelines. In addition, this report summarizes the latest information on the Immuno Polymorphism Database (IPD)-NHKIR Database, which contains annotatedKIR sequences from four non-human primate species. (Source: Immunogenetics)
Source: Immunogenetics - November 29, 2019 Category: Genetics & Stem Cells Source Type: research

Correlation between antidrug antibodies, pre-existing antidrug reactivity, and immunogenetics (MHC class II alleles) in cynomolgus macaque
AbstractImmunogenicity of biomolecules is one of the largest concerns in biological therapeutic drug development. Adverse immune responses as a result of immunogenicity to biotherapeutics range from mild hypersensitivity reactions to potentially life-threatening anaphylactic reactions and can negatively impact human health and drug efficacy. Numerous confounding patient-, product- or treatment-related factors can influence the development of an immune reaction against therapeutic proteins. The goal of this study was to investigate the relationship between pre-existing drug reactivity (PE-ADA), individual immunogenetics (MH...
Source: Immunogenetics - November 27, 2019 Category: Genetics & Stem Cells Source Type: research

The Immune Epitope Database and Analysis Resource Program 2003 –2018: reflections and outlook
AbstractThe Immune Epitope Database and Analysis Resource (IEDB) contains information related to antibodies and T cells across an expansive scope of research fields (infectious diseases, allergy, autoimmunity, and transplantation). Capture and representation of the data to reflect growing scientific standards and techniques have required continual refinement of our rigorous curation and query and reporting processes beginning with the automated classification of over 28 million PubMed abstracts, and resulting in easily searchable data from over 20,000 published manuscripts. Data related to MHC binding and elution, nonpepti...
Source: Immunogenetics - November 25, 2019 Category: Genetics & Stem Cells Source Type: research

Development and optimization of a hybridization technique to type the classical class I and class II B genes of the chicken MHC
We describe a typing protocol for classical chicken class I (BF) and class II B (BLB) genes based on a hybridization method called reference strand-mediated conformational analysis (RSCA). We optimize the various steps, validate the analysis using well-characterized chicken MHC haplotypes, apply the system to type some experimental lines and discover a new chicken class I allele. This work establishes a basis for typing the MHC genes of chickens worldwide and provides an opportunity to correlate with microsatellite and with single nucleotide polymorphism (SNP) typing for approaches involving imputation. (Source: Immunogenetics)
Source: Immunogenetics - November 25, 2019 Category: Genetics & Stem Cells Source Type: research

Evaluation of alloreactive T cells based on the degree of MHC incompatibility using flow cytometric mixed lymphocyte reaction assay in dogs
AbstractIt has become anticipated that regenerative medicine will extend into the field of veterinary medicine as new treatments for various disorders. Although the use of allogeneic stem cells for tissue regeneration is more attractive than that of autologous cells in emergencies, the therapeutic potential of allogeneic transplantation is often limited by allo-immune responses inducing graft rejection. Therefore, a methodology for quantifying and monitoring alloreactive T cells is necessary for evaluating allo-immune responses. The mixed lymphocyte reaction (MLR) is widely used to evaluate T cell alloreactivity. In human,...
Source: Immunogenetics - November 20, 2019 Category: Genetics & Stem Cells Source Type: research

Correction to: Nomenclature report 2019: major histocompatibility complex genes and alleles of great and small ape and old and new world monkey species
The original version of this article contained a spelling error in the Acknowledgments regarding the name of the funding organisation supporting GM and JAH. UKRI-BBSCR should have been UKRI-BBSRC, as is now indicated correctly below. (Source: Immunogenetics)
Source: Immunogenetics - November 19, 2019 Category: Genetics & Stem Cells Source Type: research

An overview of immunoinformatics approaches and databases linking T cell receptor repertoires to their antigen specificity
AbstractRecent advances in molecular and bioinformatic methods have greatly improved our ability to study the formation of an adaptive immune response towards foreign pathogens, self-antigens, and cancer neoantigens. T cell receptors (TCR) are the key players in this process that recognize peptides presented by major histocompatibility complex (MHC). Owing to the huge diversity of both TCR sequence variants and peptides they recognize, accumulation and complex analysis of large amounts of TCR-antigen specificity data is required for understanding the structure and features of adaptive immune responses towards pathogens, va...
Source: Immunogenetics - November 18, 2019 Category: Genetics & Stem Cells Source Type: research

A potential nomenclature for the Immuno Polymorphism Database (IPD) of chicken MHC genes: progress and problems
AbstractAmong the genes with the highest allelic polymorphism and sequence diversity are those encoding the classical class I and class II molecules of the major histocompatibility complex (MHC). Although many thousands of MHC sequences have been deposited in general sequence databases like GenBank, the availability of curated MHC sequences with agreed nomenclature has been enormously beneficial. Along with the Immuno Polymorphism Database-IMunoGeneTics/human leukocyte antigen (IPD-IMGT/HLA) database, a collection of databases for curated sequences of immune importance has been developed. A recent addition is an IPD-MHC da...
Source: Immunogenetics - November 18, 2019 Category: Genetics & Stem Cells Source Type: research

PIRCHE-II: an algorithm to predict indirectly recognizable HLA epitopes in solid organ transplantation
AbstractHuman leukocyte antigen (HLA) mismatches between donors and recipients may lead to alloreactivity after solid organ transplantation. Over the last few decades, our knowledge of the complexity of the HLA system has dramatically increased, as numerous new HLA alleles have been identified. As a result, the likelihood of alloreactive responses towards HLA mismatches after solid organ transplantation cannot easily be assessed. Algorithms are promising solutions to estimate the risk for alloreactivity after solid organ transplantation. In this review, we show that the recently developed PIRCHE-II (Predicted Indirectly Re...
Source: Immunogenetics - November 18, 2019 Category: Genetics & Stem Cells Source Type: research

Single haplotype admixture models using large scale HLA genotype frequencies to reproduce human admixture
We present a statistical method based on high-resolution HLA haplotype frequencies to resolve population admixture using a non-negative matrix factorization formalism a nd validated using haplotype frequencies from 56 world populations. The result is a minimal set of source components (SCs) decoding roughly 90% of the total variance in the studied admixtures. These SCs agree with the geographical distribution, phylogenies, and recent admixture events of the studied groups. With the growing population of multi-ethnic individuals, or individuals that do not report race/ethnic information, the HLA matching process for stem-ce...
Source: Immunogenetics - November 18, 2019 Category: Genetics & Stem Cells Source Type: research

Update 2020: nomenclature and listing of celiac disease –relevant gluten epitopes recognized by CD4 + T cells
AbstractCeliac disease is caused by an abnormal intestinal T cell response to cereal gluten proteins. The disease has a strong human leukocyte antigen (HLA) association, and CD4+ T cells recognizing gluten epitopes presented by disease-associated HLA-DQ allotypes are considered to be drivers of the disease. This paper provides an update of the currently known HLA-DQ restricted gluten T cell epitopes with their names and sequences. (Source: Immunogenetics)
Source: Immunogenetics - November 18, 2019 Category: Genetics & Stem Cells Source Type: research

An Illumina approach to MHC typing of Atlantic salmon
AbstractThe IPD-MHC Database represents the official repository for non-human major histocompatibility complex (MHC) sequences, overseen and supported by the Comparative MHC Nomenclature Committee, providing access to curated MHC data and associated analysis tools. IPD-MHC gathers allelic MHC class I and class II sequences from classical and non-classical MHC loci from various non-human animals including pets, farmed and experimental model animals. So far, Atlantic salmon and rainbow trout are the only teleost fish species with MHC class I and class II sequences present. For the remaining teleost or ray-finned species, dat...
Source: Immunogenetics - November 12, 2019 Category: Genetics & Stem Cells Source Type: research

Two novel HLA-DQ2.5-restricted gluten T cell epitopes in the DQ2.5-glia- γ4 epitope family
AbstractCeliac disease is a chronic inflammatory condition of the small intestine caused by aberrant adaptive immune response to gluten protein from wheat and related cereal plants. Over 90% of celiac disease patients carry the HLA-DQ2.5 allotype and HLA-DQ2.5 presents gluten peptides to gluten-reactive CD4+ T cells in celiac disease patients. A large number of HLA-DQ2.5-restricted gluten T cell epitopes have been identified over the years. These epitopes are in general proline-rich and contain at least one glutamic acid residue that is generated from glutamine in the native gluten protein by deamidation. The deamidation i...
Source: Immunogenetics - November 1, 2019 Category: Genetics & Stem Cells Source Type: research

The IPD Project: a centralised resource for the study of polymorphism in genes of the immune system
AbstractThe Immuno Polymorphism Database (IPD), https://www.ebi.ac.uk/ipd/, is a set of specialist databases that enable the study of polymorphic genes which function as part of the vertebrate immune system. The major focus is on the hyperpolymorphic major histocompatibility complex (MHC) genes and the killer-cell immunoglobulin-like receptor (KIR) genes, by providing the official repository and primary source of sequence data. Databases are centred around humans as well as animals important for food security, for companionship and as disease models. The IPD project works with specialist groups or nomenclature committees w...
Source: Immunogenetics - October 22, 2019 Category: Genetics & Stem Cells Source Type: research

Nomenclature report 2019: major histocompatibility complex genes and alleles of Great and Small Ape and Old and New World monkey species
AbstractThe major histocompatibility complex (MHC) is central to the innate and adaptive immune responses of jawed vertebrates. Characteristic of the MHC are high gene density, gene copy number variation, and allelic polymorphism. Because apes and monkeys are the closest living relatives of humans, the MHCs of these non-human primates (NHP) are studied in depth in the context of evolution, biomedicine, and conservation biology. The Immuno Polymorphism Database (IPD)-MHC NHP Database (IPD-MHC NHP), which curates MHC data of great and small apes, as well as Old and New World monkeys, has been upgraded. The curators of the da...
Source: Immunogenetics - October 17, 2019 Category: Genetics & Stem Cells Source Type: research

Nomenclature report on the major histocompatibility complex genes and alleles of the laboratory rat ( Rattus norvegicus )
AbstractThe laboratory rat (Rattus norvegicus) has a long tradition as experimental animal in transplantation and autoimmunity research and, hence, there has been an inherent interest in its major histocompatibility complex (MHC), the RT1 complex. Available inbred rat strains and their derived RT1-congenic and intra-RT1 recombinant congenic strains were crucial for definition and characterization of RT1 genes and alleles and essentially advanced elucidation of the RT1 genomic organization in the past. The Immuno Polymorphism Database (IPD) harbors a section for rat MHC genes and alleles (IPD-MHC RT1) since 2005. The curato...
Source: Immunogenetics - September 14, 2019 Category: Genetics & Stem Cells Source Type: research

Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft
AbstractHuman CD4+ T lymphocytes play an important role in inducing potent immune responses. T cells are activated and stimulated by peptides presented in human leucocyte antigen (HLA)-class II molecules. These HLA-class II molecules typically present peptides of between 12 and 20 amino acids in length. The region that interacts with the HLA molecule, designated as the peptide-binding core, is highly conserved in the residues which anchor the peptide to the molecule. In addition, as these peptides are the product of proteolytic cleavages, certain conserved residues may be expected at the N- and C-termini outside the bindin...
Source: Immunogenetics - September 13, 2019 Category: Genetics & Stem Cells Source Type: research

Can extreme MHC class I diversity be a feature of a wide geographic range? The example of Seba ’s short-tailed bat ( Carollia perspicillata )
AbstractThe major histocompatibility complex (MHC) is one of the most diverse genetic regions under pathogen-driven selection because of its central role in antigen binding and immunity. The highest MHC variability, both in terms of the number of individual alleles and gene copies, has so far been found in passerine birds; this is probably attributable to passerine adaptation to both a wide geographic range and a diverse array of habitats. If extraordinary high MHC variation and duplication rates are adaptive features under selection during the evolution of ecologically and taxonomically diverse species, then similarly div...
Source: Immunogenetics - September 13, 2019 Category: Genetics & Stem Cells Source Type: research

Divergence between genes but limited allelic polymorphism in two MHC class II A genes in Leach ’s storm-petrels Oceanodroma leucorhoa
AbstractThe major histocompatibility complex (MHC) is critical to host-pathogen interactions. Class II MHC is a heterodimer, with α and β subunits encoded by different genes. The peptide-binding groove is formed by the first domain of both subunits (α1 and β1), but studies of class II variation or natural selection focus primarily on the β subunit and II B genes. We explored MHC II A in Leach’s storm-petrel, a seabird with two expressed, polymorphic II B genes. We found two II A genes,Ocle-DAA andOcle-DBA, in contrast to the single II A gene in chicken and duck. In exon 2 which encodes the ...
Source: Immunogenetics - September 10, 2019 Category: Genetics & Stem Cells Source Type: research

How does the immune system learn to distinguish between good and evil? The first definitive studies of T cell central tolerance and positive selection
AbstractDemonstration that immature CD4  + 8+ thymocytes contain T cell precursors that are subjected to positive and negative selection was the major step towards understanding how the adaptive immune system acquires the ability to distinguish foreign or abnormal (mutated or infected) self-cells from normal (healthy) cells. In the pr esent review, the roles of TCR, CD4, CD8, and MHC molecules in intrathymic selection and some of the crucial experiments that contributed to the solution of the great immunological puzzle of self/nonself discrimination are described in an historical perspective. Recently, these ...
Source: Immunogenetics - August 15, 2019 Category: Genetics & Stem Cells Source Type: research

Analysis of macaque BTN3A genes and transcripts in the extended MHC: conserved orthologs of human γδ T cell modulators
AbstractButyrophilins (BTN), specifically BTN3A, play a central role in the modulation of γδ T cells, which are mainly present in gut and mucosal tissues. BTN3A1 is known, for example, to activate Vγ9Vδ2 T cells by means of a phosphoantigen interaction. In the extended HLA region, three genes are located, designatedBTN3A1,BTN3A2 andBTN3A3, which were also defined in rhesus macaques. In contrast to humans, rhesus monkeys have an additional gene,BTN3A3Like, which has the features of a pseudogene. cDNA analysis of 32 Indian rhesus and 16 cynomolgus macaques originating from multiple-generation families...
Source: Immunogenetics - August 5, 2019 Category: Genetics & Stem Cells Source Type: research

MHC genotyping from rhesus macaque exome sequences
AbstractIndian rhesus macaque major histocompatibility complex (MHC) variation can influence the outcomes of transplantation and infectious disease studies. Frequently, rhesus macaques are MHC genotyped to identify variants that could account for unexpected results. Since the MHC is only one region in the genome where variation could impact experimental outcomes, strategies for simultaneously profiling variation in the macaque MHC and the remainder of the protein coding genome would be useful. Here we determine MHC class I and class II genotypes using target-capture probes enriched for MHC sequences, a method we term macaq...
Source: Immunogenetics - July 18, 2019 Category: Genetics & Stem Cells Source Type: research

Methylation of H3K27 and H3K4 in key gene promoter regions of thymus in RA mice is involved in the abnormal development and differentiation of iNKT cells
AbstractEpigenetic modifications have been shown to be important for immune cell differentiation by regulating gene transcription. However, the role and mechanism of histone methylation in the development and differentiation of iNKT cells in rheumatoid arthritis (RA) mice have yet to be deciphered. The DBA/1 mouse RA model was established by using a modified GPI mixed peptide. We demonstrated that total peripheral blood, thymus, and spleen iNKT cells in RA mice decreased significantly, while iNKT1 in the thymus and spleen was increased significantly. PLZF protein and PLZF mRNA levels were significantly decreased in thymus ...
Source: Immunogenetics - July 11, 2019 Category: Genetics & Stem Cells Source Type: research

Examining epitope mutagenesis as a strategy to reduce and eliminate human antibody binding to class II swine leukocyte antigens
AbstractXenotransplantation of pig organs into people may help alleviate the critical shortage of donors which faces organ transplantation. Unfortunately, human antibodies vigorously attack pig tissues preventing the clinical application of xenotransplantation. The swine leukocyte antigens (SLA), homologs of human HLA molecules, can be xenoantigens. SLA molecules, encoded by genes in the pig major histocompatibility complex, contribute to protective immune responses in pig. Therefore, simply inactivating them through genome engineering could reduce the ability of the human immune system to surveil transplanted pig organs f...
Source: Immunogenetics - July 4, 2019 Category: Genetics & Stem Cells Source Type: research

The microstructure in the placenta is influenced by the functional diversity of HLA-G allelic variants
AbstractThe main expression sites of HLA-G are human extravillous trophoblast cells. The interaction of HLA-G with uterine NK cells promotes their maturation and differentiation into decidual NK (dNK) cells. dNK cells secrete chemokines, cytokines, and proangiogenic factors in favor of a vascular remodeling and an immune suppressive microenvironment of the decidua. HLA-G is the most polymorphic member of the oligomorphic non-classical HLA molecule family; yet, the impact of polymorphic differences is not comprehensively understood. sHLA-G levels in embryo culture medium correlate with successful pregnancy; however, it rema...
Source: Immunogenetics - June 27, 2019 Category: Genetics & Stem Cells Source Type: research

Improved peptide-MHC class II interaction prediction through integration of eluted ligand and peptide affinity data
AbstractMajor histocompatibility complex (MHC) class II antigen presentation is a key component in eliciting a CD4+ T cell response. Precise prediction of peptide-MHC (pMHC) interactions has thus become a cornerstone in defining epitope candidates for rational vaccine design. Current pMHC prediction tools have, so far, primarily focused on inference from in vitro binding affinity. In the current study, we collate a large set of MHC class II eluted ligands generated by mass spectrometry to guide the prediction of MHC class II antigen presentation. We demonstrate that models developed on eluted ligands outperform those devel...
Source: Immunogenetics - June 10, 2019 Category: Genetics & Stem Cells Source Type: research

Transcript analysis reveals the involvement of NF- κB transcription factors for the activation of TGF-β signaling in nematode-infected Drosophila
This study explores the cross-talk between the well-characterized nuclear factor kappa B (NF- κB) innate immune signaling pathways and transforming growth factor beta (TGF-β) signaling pathway in response to parasitic nematode infection inDrosophila. To understand the link between signaling pathways, we followed on our previous studies by performing a transcript-level analysis of different TGF- β signaling components following infection of immune-compromisedDrosophila adult flies with the nematode parasitesHeterorhabditis gerrardi andH. bacteriophora. Our findings demonstrate the requirement of NF- κB...
Source: Immunogenetics - May 30, 2019 Category: Genetics & Stem Cells Source Type: research

Correction to: Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab
The authors regret that the online version of this article contains an error. TheMBD4 mutation in sample MM138 was given an incorrect dbSNP ID. The correct ID is rs769076971. (Source: Immunogenetics)
Source: Immunogenetics - May 30, 2019 Category: Genetics & Stem Cells Source Type: research

Conservation of molecular and cellular phenotypes of invariant NKT cells between humans and non-human primates
AbstractInvariant NKT (iNKT) cells in both humans and non-human primates are activated by the glycolipid antigen, α-galactosylceramide (α-GalCer). However, the extent to which the molecular mechanisms of antigen recognition and in vivo phenotypes of iNKT cells are conserved among primate species has not been determined. Using an evolutionary genetic approach, we found a lack of diversifying selection in CD1 g enes over 45 million years of evolution, which stands in stark contrast to the history of the MHC system for presenting peptide antigens to T cells. The invariant T cell receptor (TCR)-α chain was st...
Source: Immunogenetics - May 23, 2019 Category: Genetics & Stem Cells Source Type: research

Identification and characterization of the lamprey cathepsin genes
AbstractCathepsins are key mammalian proteases that play an important role in the immune response. Several studies have revealed the versatile and critical functions of cathepsins. Here, we obtained ten kinds of cathepsin homologs and identified seven homologs with complete coding sequences. Phylogenetic analysis verified their identities and supported the classification of cathepsins into seven families, which is similar to other vertebrates. Tissue-specific expression analysis showed that all lamprey cathepsins (L-cathepsins) are present in the supraneural body (SB), kidney, gill, intestine, brain, heart, and liver, but ...
Source: Immunogenetics - May 14, 2019 Category: Genetics & Stem Cells Source Type: research

Convergent inactivation of the skin-specific C-C motif chemokine ligand 27 in mammalian evolution
AbstractThe appearance of mammalian-specific skin features was a key evolutionary event contributing for the elaboration of physiological processes such as thermoregulation, adequate hydration, locomotion, and inflammation. Skin inflammatory and autoimmune processes engage a population of skin-infiltrating T cells expressing a specific C-C chemokine receptor (CCR10) which interacts with an epidermal CC chemokine, the skin-specific C-C motif chemokine ligand 27 (CCL27). CCL27 is selectively produced in the skin by keratinocytes, particularly upon inflammation, mediating the adhesion and homing of skin-infiltrating T cells. ...
Source: Immunogenetics - May 2, 2019 Category: Genetics & Stem Cells Source Type: research

Immune stimulation of rainbow trout reveals divergent regulation of MH class II-associated invariant chain isoforms
AbstractMajor histocompatibility complex (MHC) class II-associated invariant chain is a chaperone responsible for targeting the MHC class II dimer to the endocytic pathway, thus enabling the loading of exogenous antigens onto the MHC class II receptor. In the current study, in vivo and in vitro methods were used to investigate the regulation of the rainbow trout invariant chain proteins S25-7 and INVX, upon immune system activation. Whole rainbow trout and the macrophage/monocyte-like cell line RTS11 were treated with PMA at concentrations shown to induce IL-1 β transcripts and homotypic aggregation of RTS11. S25-7 tr...
Source: Immunogenetics - April 29, 2019 Category: Genetics & Stem Cells Source Type: research

Correction to: HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues
The original version of this article contained errors. The Article Title, Figures 1 and 3, and Electronic Supplementary Materials were incorrectly shown in the wrong version. The original article has been corrected. (Source: Immunogenetics)
Source: Immunogenetics - April 24, 2019 Category: Genetics & Stem Cells Source Type: research

DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs
AbstractAddison ’s disease (AD) is a life-threatening endocrine disorder that occurs spontaneously in both humans and dogs. Associations between MHC class II genes and AD have been shown in several human studies. Our goal was to identify MHC class II associations with AD in a large population of Standard Poodles, a breed highly predisposed to AD. We sequenced exon 2 of the class II genes DLA-DRB1, DLA-DQA1, and DLA-DQB1 in 110 affected and 101 unaffected Standard Poodles and tested for association with AD. After correcting for population structure, two haplotypes were found to confer risk of developing AD i n a sex-s...
Source: Immunogenetics - April 9, 2019 Category: Genetics & Stem Cells Source Type: research

HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues
In this study, we were able to recover stable pHLA-F*01:01 complexes and analyze the characteristics of peptides naturally presented by HLA-F. These HLA-F-restricted peptides exhibit a non-canonical length without a defined N-terminal anchor. The peptide characteristics lead to a unique presentation profile and influence the stability of the protein. Furthermore, we demonstrate that almost all source proteins of HLA-F-restricted peptides are described to interact with HIV proteins. Understanding the balance switch between HLA-Ia and HLA-F expression and peptide selection will support to understand the role of HLA-F in vira...
Source: Immunogenetics - April 2, 2019 Category: Genetics & Stem Cells Source Type: research

HLA-F*01:01-restricted peptides reveal to prefer a length of 16 amino acids with N-terminal flexibility
In this study, we were able to recover stable pHLA-F*01:01 complexes and analyze the characteristics of peptides naturally presented by HLA-F. These HLA-F-restricted peptides exhibit a non-canonical length without a defined N-terminal anchor. The peptide characteristics lead to a unique presentation profile and influence the stability of the protein. Furthermore, we demonstrate that almost all source proteins of HLA-F-restricted peptides are described to interact with HIV proteins. Understanding the balance switch between HLA-Ia and HLA-F expression and peptide selection will support to understand the role of HLA-F in vira...
Source: Immunogenetics - April 2, 2019 Category: Genetics & Stem Cells Source Type: research

Distribution of ancient α1 and α2 domain lineages between two classical MHC class I genes and their alleles in grass carp
AbstractMajor histocompatibility complex (MHC) class I molecules play a crucial role in the immune response by binding and presenting pathogen-derived peptides to specific CD8+ T cells. From cDNA of 20 individuals of wild grass carp (Ctenopharyngodon idellus), we could amplify one or two alleles each of classical MHC class I genesCtid-UAA andCtid-UBA. In total, 27 and 22 unique alleles ofCtid-UAA andCtid-UBA were found. The leader, α1, transmembrane and cytoplasmic regions distinguish betweenCtid-UAA andCtid-UBA, and their encoded α1 domain sequences belong to the ancient lineages α1-V and α1-II, re...
Source: Immunogenetics - April 2, 2019 Category: Genetics & Stem Cells Source Type: research

Strong selection of the TLR2 coding region among the Lagomorpha suggests an evolutionary history that differs from other mammals
AbstractToll-like receptors (TLRs) are one of the first lines of defense against pathogens and are crucial for triggering an appropriate immune response. AmongTLRs,TLR2 is functional in all vertebrates and has high ability in detecting bacterial and viral pathogen ligands. The mammals ’ phylogenetic tree ofTLR2 showed longer branches for the Lagomorpha clade, raising the hypothesis that lagomorphs experienced an acceleration of the mutation rate. This hypothesis was confirmed by (i) Tajima ’s test of neutrality that revealed different evolutionary rates between lagomorphs and the remaining mammals with lagomorp...
Source: Immunogenetics - March 14, 2019 Category: Genetics & Stem Cells Source Type: research

Characterisation of major histocompatibility complex class IIa haplotypes in an island sheep population
AbstractThe ovine MHC class IIa is known to consist of six to eight loci located in close proximity on chromosome 20, forming haplotypes that are typically inherited without recombination. Here, we characterise the class IIa haplotypes within the Soay sheep (Ovis aries) on St. Kilda to assess the diversity present within this unmanaged island population. We used a stepwise sequence-based genotyping strategy to identify alleles at seven polymorphic MHC class IIa loci in a sample of 118 Soay sheep from four cohorts spanning 15  years of the long-term study on St. Kilda.DRB1, the most polymorphic MHC class II locus, was ...
Source: Immunogenetics - February 22, 2019 Category: Genetics & Stem Cells Source Type: research

Functional variation at an expressed MHC class II β locus associates with Ranavirus infection intensity in larval anuran populations
AbstractInfectious diseases are causing catastrophic losses to global biodiversity. Iridoviruses in the genusRanavirus are among the leading causes of amphibian disease-related mortality. Polymorphisms in major histocompatibility complex (MHC) genes are significantly associated with variation in amphibian pathogen susceptibility. MHC genes encode two classes of polymorphic cell-surface molecules that can recognize and bind to diverse pathogen peptides. While MHC class I genes are the classic mediators of viral-acquired immunity, larval amphibians do not express them. Consequently, MHC class II gene diversity may be an impo...
Source: Immunogenetics - February 13, 2019 Category: Genetics & Stem Cells Source Type: research

Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab
AbstractThere is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-functionMBD4 mutation. Here, we report on another UM patient who carried anMBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a fivefold higher than average mutation burden. We confirmed the association between germline loss-of-function variant inMBD4 and CI response. The patient experienced stable disease (10  months) and survived 2 years wit...
Source: Immunogenetics - February 4, 2019 Category: Genetics & Stem Cells Source Type: research

Class I transactivator, NLRC5: a central player in the MHC class I pathway and cancer immune surveillance
AbstractMajor histocompatibility complex (MHC) class I and class II molecules play critical roles in the activation of the adaptive immune system by presenting antigens to CD8+ and CD4+ T cells, respectively. Although it has been well known that CIITA (MHC class II transactivator), an NLR (nucleotide-binding domain, leucine-rich-repeat containing) protein, as a master regulator of MHC class II gene expression, the mechanism of MHC class I gene transactivation was unclear. Recently, another NLR protein, NLRC5 (NLR family, CARD domain-containing 5), was identified as an MHC class I transactivator (CITA). NLRC5 is a critical ...
Source: Immunogenetics - January 31, 2019 Category: Genetics & Stem Cells Source Type: research

Biology, evolution, and history of antigen processing and presentation: Immunogenetics special issue 2019
(Source: Immunogenetics)
Source: Immunogenetics - January 31, 2019 Category: Genetics & Stem Cells Source Type: research

A personal retrospective on the mechanisms of antigen processing
AbstractMy intention here is to describe the history of the molecular aspects of the antigen processing field from a personal perspective, beginning with the early identification of the species that we now know as MHC class I and MHC class II molecules, to the recognition that their stable surface expression and detection by T cells depends on peptide association, and to the unraveling of the biochemical and cell biological mechanisms that regulate peptide binding. One goal is to highlight the role that serendipity or, more colloquially, pure blind luck can play in advancing the research enterprise when it is combined with...
Source: Immunogenetics - January 29, 2019 Category: Genetics & Stem Cells Source Type: research

What to do with HLA-DO/H-2O two decades later?
AbstractThe main objective of antigen processing is to orchestrate the selection of immunodominant epitopes for recognition by CD4 T cells. To achieve this, MHC class II molecules have evolved with a flexible peptide-binding groove in need of a bound peptide. Newly synthesized MHC-II molecules bind a class II invariant chain (Ii) upon synthesis and are shuttled to a specialized compartment, where they encounter exogenous antigens. Ii serves multiple functions, one of which is to maintain the shape of the MHC-II groove so that it can readily bind exogenous antigens upon dissociation of the Ii peptide in MHC- II compartment....
Source: Immunogenetics - January 26, 2019 Category: Genetics & Stem Cells Source Type: research

Origin and evolution of the specialized forms of proteasomes involved in antigen presentation
AbstractProteasomes are a multi-subunit protease complex that produces peptides bound by major histocompatibility complex (MHC) class I molecules. Phylogenetic studies indicate that two specialized forms of proteasomes, immunoproteasomes and thymoproteasomes, and the proteasome activator PA28 αβ emerged in a common ancestor of jawed vertebrates which acquired adaptive immunity based on the MHC, T cell receptors, and B cell receptors ~ 500 million years ago. Comparative genomics studies now provide strong evidence that the genes coding for the immunoproteasome subunits emerged by geno me-wide duplication. ...
Source: Immunogenetics - January 24, 2019 Category: Genetics & Stem Cells Source Type: research

Exploring the etiopathogenesis of systemic lupus erythematosus: a genetic perspective
AbstractSystemic lupus erythematosus (SLE) is an autoimmune multi-organ disorder that presents itself in a thousand ways. Its clinical course is extremely unpredictable, which makes diagnosis and treatment a challenge for clinicians. It appears that the clinical course of SLE is determined by genetic material in combination with environmental factors. In this article, we review recent findings on the pathogenesis of SLE from the perspective of genetics, focusing on defects in the clearance of apoptotic bodies and immune complexes, on alterations in the innate immune system response, and on impaired pathways in the adaptive...
Source: Immunogenetics - January 22, 2019 Category: Genetics & Stem Cells Source Type: research