FUNCTIONAL CONSEQUENCES OF THE BINDING OF MHC CLASS II-DERIVED PEPTIDES TO MHC CLASS-II

Three MHC class II-derived synthetic peptides (I-A(beta)(g7)1-16, I-A( beta)(g7)52-77 and I-A(alpha)(g7)63-82YC) were analyzed for their abil ity to bind to syngeneic and allogeneic MHC class II molecules using a whole cell, competitive peptide binding assay, These studies demonstr ated that the A(beta)(g7)1-16 peptide was able to specifically bind to syngeneic as well as to four allogeneic MHC class II molecules. The A (alpha)(g7)63-82YC peptide bound to self MHC class II molecules with a lower relative affinity and was able to bind to three out of the four allogeneic cells tested, The binding of the three I-A(g7)-derived pep tides to the self MHC class II was functionally significant, The A(bet a)(g7)1-16 and A(beta)(g7)52-77 peptides inhibited the proliferation o f a heat shock protein 60 peptide-specific T(h)1 clone by MHC blockade , Interestingly, the A(alpha)(g7)63-82YC peptide appeared to interact directly with T cells as pretreatment of the T(h)1 clone with this pep tide resulted in inhibition of antigen-induced proliferation. This phe nomenon was analyzed in more detail and it was found that this peptide could behave as a partial agonist. Incubation of T cells with the A(a lpha)(g7)63-82YC peptide resulted in up-regulation of IL-2R alpha chai n expression and induction of IFN-gamma secretion. In addition T cells pretreated with this peptide were rendered hyporesponsive to further antigenic stimulation. Thus, a peptide derived from MHC class II may b e used in an immunoregulatory capacity.