Processing of viable group A streptococci leads to major histocompatibility complex class II presentation of T cell epitopes from the major protective antigen.

We have previously mapped major histocompatibility complex (MHC) class II-restricted T cell epitopes of the surface M protein of type 5 group A streptococci (M5) and show here that two out of four epitopes investigated were efficiently processed during incubation of viable streptococci with spleen cells for presentation to M5-specific murine T cell clones. Viable streptococci were processed more efficiently than heat-killed bacteria suggesting that secreted virulence factors of streptococci do not obstruct processing of streptococcal antigens in the dose range used. Epitopes from different regions of M5 could be ranked according to the efficiency with which they were processed, which may contribute to their relative immunodominance. It was further demonstrated that T cell clones specific for M5 308-319, an epitope from the M type conserved carboxy-terminal half of M5, cross-reacted between M5, M6 and M12, but not M49, streptococci. Helper T cell epitopes which are shared between streptococcal M types and are presented by MHC class II molecules on antigen-presenting cells after processing of viable streptococci could be particularly useful in the design of multivalent streptococcal vaccines.