CARBOXY-TERMINAL RESIDUES OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-ASSOCIATED PEPTIDES CONTROL THE PRESENTATION OF THE BACTERIAL SUPERANTIGEN TOXIC SHOCK SYNDROME TOXIN-1 TO T-CELLS

Previous studies have shown that the presentation of some bacterial su perantigens by major histocompatibility complex (MHC) class II molecul es is strongly influenced by class II-associated peptides. For example , presentation of the toxic shock syndrome toxin-l (TSST-1) superantig en by antigen-processing-defective T2-I-A(b) cells (which expresses I- A(b) that is either empty or associated with invariant chain-derived p eptides) can be strongly enhanced by some, but not other, I-Ab-binding peptides. Here we investigate the contribution of I-A(b)-associated p eptides in the presentation of TSST-1 to T cells. The data show that o verlapping peptides expressing the same core I-A(b)-restricted epitope , but with various N and C termini, can differ profoundly in their abi lity to promote TSST-1 presentation to T cells. Analysis of altered an d truncated peptides indicates that residues at the C-terminal end of the peptide have a dramatic effect on TSST-1 presentation. This effect does not involve a cognate interaction between the peptide and the TS ST-1 molecule, but appears to depend on the length of the C-terminal r egion. These data are consistent with crystallographic studies suggest ing that TSST-1 may interact with the C-terminal residues of MHC class II-associated peptides. We also examined the capacity of naturally pr ocessed peptides to promote TSST-1 binding using a superantigen blocki ng assay. The data demonstrated that a naturally processed epitope is dominated by peptides that do not promote strong TSST-1 binding to I-B h. Taken together, these data suggest that TSST-1 binding to MHC class II molecules is controlled by the C-terminal residues of the associat ed peptide, and that many naturally processed peptide/class II complex es do not present TSST-1 to T cells. Thus, the peptide dependence of T SST-1 binding to class II molecules may significantly reduce the capac ity of TSST-1 to stimulate T cells.