CHARACTERIZATION OF UNIQUE HUMAN TCR V-BETA SPECIFICITIES FOR A FAMILY OF STREPTOCOCCAL SUPERANTIGENS REPRESENTED BY RHEUMATOGENIC SEROTYPES OF M-PROTEIN

The M protein of Streptococcus pyogenes plays a major role in the viru lence of these bacteria. Members of. the M protein superfamily are cha racterized by the presence of tandem segments of repeated amino acid s equences. The NH2-terminal end of the M proteins is a hypervariable re gion that harbors the type-specific epitopes of the molecule. Pepsin c leaves the molecule into a highly conserved carboxyl terminal half and a variable amino terminal portion referred to as pep M. In some indiv iduals, infection with certain serotypes of group A streptococci is fo llowed by autoimmune disorders such as rheumatic fever and acute glome rulonephritis. The serotypes of M protein that show a high degree of a ssociation with acute rheumatic fever are referred to as rheumatogenic serotypes. We have reported that one such serotype, type 5, is a supe rantigen to human T cells, specifically stimulating T cells bearing V beta 2, V beta 4, and V beta 8 elements. Here we extend our studies by examining other rheumatogenic serotypes for superantigenic properties . Studies with types 6, 18, 19, and 24 M proteins revealed that they a re all superantigens to human T cells. The specificity to V beta 4 was shared by the rheumatogenic M proteins tested; however, each pep M se rotype has its unique characteristic set of V beta specificity and the se are distinct from those reported for the streptococcal pyrogenic ex otoxins. The non-rheumatogenic serotype, pep M2, only stimulated V bet a 2-bearing T cells. This study establishes that the structurally rela ted M proteins represent a family of streptococcal superantigens analo gous to the structurally related family of staphylococcal enterotoxin superantigens.