STREPTOCOCCUS-PYOGENES TYPE-5M PROTEIN IS AN ANTIGEN, NOT A SUPERANTIGEN, FOR HUMAN T-CELLS

M proteins are coiled-coil dimers expressed on group A streptococcal c ell surfaces. They have an important role in host antistreptococcal im munity and in poststreptococcal autoimmune sequelae. Controversy has a risen regarding whether type 5 M proteins are superantigenicity for hu man T cells. To investigate this, we have produced and tested M5 in th e form of two novel recombinant proteins. We found no evidence of supe rantigenicity using either recombinant whole M5 protein (rM5) or recom binate pep M5 protein (rpepM5) to activate peripheral blood mononuclea r cells (PBMC) from healthy adult volunteers. Short-term, rM5-specific T-cell lines from different subjects were uniformly self-APC restrict ed and showed no consistent pattern of TCR V beta usage. A synthetic p eptide of M5 residues 217-237 was found to contain epitope(s) recogniz ed by some rM5-specific human T cells. PBMC responses to rM5 and rpepM 5 in 3- and 7-day proliferation assays were characteristic of antigeni c rather than superantigenic stimulation. We conclude that type 5 M pr otein activates human T cells as a conventional antigen. (C) American Society for Histocompatibility and Immunogenetics, 1997.