An analysis of synthetic peptide restriction by HLA-DR alleles in T cells from human subjects, naturally sensitized by Streptococcus mutans.

T cells from most human subjects show significant in vitro proliferative responses to a 185-kDa surface Ag from Streptococcus mutans as well as to synthetic peptides derived from the sequence of a Mr 3800 streptococcal Ag. T cells from subjects expressing each of the alleles from DR1 to DR7 responded to synthetic peptides of 17 or 21 amino acid residues. Furthermore, inhibition studies with mAb to HLA class I and class II Ag showed that the DR Ag was a restriction molecule for the proliferative responses. Mouse L cells transfected with DR1, DR2, DR4, DR5, and DR7 were used to confirm the permissive nature of the responses. An analysis of the fine specificity of the responses showed that the minimum peptides capable of stimulating T cells from subjects with different DR types varied by one or two residues. For DR2 and DR3 the shortest peptide was residues 6-15, an additional serine (residue 5) was required for DR1 and DR7 and an aspartic acid (residue 4) for DR4, DR5, and DR6. Successful oral-mucosal bacterial colonisation in humans, by a largely commensal Streptococcus, might be associated with the permissive nature of the HLA-DR restriction of the response to a major streptococcal cell surface peptide. The peptide recognised in association with the HLA-DR molecule may induce an immune response that prevents central entry of the organism from the peripheral mucosal site.