ROLE OF HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX DQ MOLECULES IN SUPERANTIGENICITY OF STREPTOCOCCUS-DERIVED PROTEIN

Antigenicity of peptic extract from type 12 group A streptococci (PEAS T12) for T cells was examined in major histocompatibility complex (MHC ) class II transgenic mice. PEAST12 was mitogenic for murine T cells w hen antigen-presenting cells were obtained from human MHC (HLA)-DQ4 al pha beta transgenic mice or from DQ6 alpha beta transgenic mice but wa s not mitogenic in DR alpha transgenic, DR51 alpha beta transgenic, Ec u transgenic, or nontransgenic mice. In addition, PEAST12 showed mitog enicity for murine T cells in DQ4 alpha singly transgenic mice but not in DQ4 beta singly transgenic mice. T-cell stimulation by PEAST12 was unrestricted by but dependent on the expression of HLA-DQ molecules o n antigen-presenting cells, and PEAST12 selectively activated T-cell r eceptor V beta 11-, V beta 15-, and V beta 18-positive T cells in mice . We propose that PEAST12 contains a superantigen which binds preferen tially to the alpha-chain of HLA-DQ molecules. The well-known phenomen on that peptic extracts from group A streptococci are mitogenic in hum ans but not in mice is likely due to structural differences in MHC cla ss II molecules between these two species of mammals.