Class II human leukocyte antigens (HLA-II) are cell surface alpha beta heterodimers (M(r) approximately 60,000) that play a pivotal role in the immune response by presenting peptides derived from environmental antigens to the T-cell receptor. A 167-171 fragment of the beta 2-chain of the HLA-DQ molecule consists of the sequence RGDVY, which is very similar to thymopentin (pentapeptide RKDVY, an active fragment (32-36) of thymopoietin, an immune system activator produced in thymi), and at the same time contains the RGD sequence, known as an inhibitor of adhesion processes. We synthesized and investigated the immunomodulatory activity of series of peptide fragments of HLA-DQ containing thymopentin-like sequences. The results indicate that all synthesized peptides suppress the cellular immune response. However, RGDV, RGDVY and QRGDVY show very weak stimulatory activity in humoral immunological response tests. In contrast to the shorter peptides, the nonapeptide fragment of HLA-DQ, TPQRGDVYT, shows significant immunosuppressive activity in all tests. A possible role of these fragments of the polypeptide chain of HLA-DQ in the regulation of HLA functions is discussed.
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