SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.

SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes. Clin Immunol. 2020 Jun 03;:108485 Authors: Sandigursky S, Philips M, Mor A Abstract T cell co-stimulation is important for the maintenance of immunologic tolerance. Co-inhibitory receptors including programmed cell death-1 (PD-1) confer peripheral tolerance to prevent autoimmunity. SAP (SH2D1A) is an adaptor molecule that is important in T cell signaling and has been shown to interact with signaling lymphocytic activation molecule (SLAM) family receptors also in the context of self-tolerance. We recently reported that SAP interferes with PD-1 function. In the current study, we investigated the levels of SAP and PD-1 in patients with rheumatoid arthritis (RA) to further understand what role they play in disease activity. We observed increased SAP levels in lymphocytes of RA patients and found that PD-1 levels correlated positively with RA disease activity. Additionally, we found that SAP interacts with CD28 to inhibit T cell signaling in vitro. This work demonstrates a putative molecular mechanism for SAP mediated PD-1 inhibition. PMID: 32504780 [PubMed - as supplied by publisher]
Source: Clinical Immunology - Category: Allergy & Immunology Authors: Tags: Clin Immunol Source Type: research