CD3 downregulation identifies high-avidity human CD8 T cells

Clin Exp Immunol. 2023 Nov 9:uxad124. doi: 10.1093/cei/uxad124. Online ahead of print.ABSTRACTCD8 T cells recognize infected and cancerous cells via their T cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modelling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context.PMID:37950348 | DOI:10.1093/cei/uxad124

Source: Clinical and Developmental Immunology - November 11, 2023 Category: Allergy & Immunology Authors: Genevieve T Clutton Ann Marie K Weideman Melissa A Mischell Sallay Kallon Shayla Z Conrad Fiona R Shaw Joanna Warren Lin Lin JoAnn D Kuruc Yinyan Xu Cynthia Gay Paul M Armistead Michael Hudgens Nilu P Goonetilleke Source Type: research