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Processing of viable group A streptococci leads to major histocompatibility complex class II presentation of T cell
B A Rossiter1, C Alfonso, M A Kehoe
1Department of Immunology, University of Newcastle upon Tyne, GB.
Abstract:
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.
Insights
Group A Streptococcus (GAS) M protein epitopes are processed efficiently by viable bacteria, aiding vaccine development. Some epitopes cross-react between different M types, suggesting potential for broad protection.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Group A Streptococcus (GAS) M protein is crucial for virulence and serotype differentiation.
- Major histocompatibility complex (MHC) class II-restricted T cell epitopes of M protein are key targets for adaptive immunity.
- Understanding antigen processing is vital for designing effective vaccines.
Purpose of the Study:
- To investigate the processing efficiency of M protein epitopes from type 5 GAS (M5) by antigen-presenting cells.
- To determine if viable or heat-killed bacteria are processed more effectively.
- To assess the cross-reactivity of specific T cell epitopes between different GAS M types for vaccine potential.
Main Methods:
- Incubation of viable and heat-killed M5 streptococci with murine spleen cells.
- Presentation of processed antigens to M5-specific murine T cell clones.
- Analysis of T cell clone responses to assess epitope processing and cross-reactivity.
Main Results:
- Two of four investigated M5 epitopes were efficiently processed from viable streptococci.
- Viable streptococci were processed more efficiently than heat-killed bacteria.
- An epitope (M5 308-319) showed cross-reactivity between M5, M6, and M12 strains, but not M49.
Conclusions:
- Efficient processing of streptococcal antigens by viable bacteria suggests virulence factors do not inhibit this process.
- Epitope processing efficiency may correlate with immunodominance.
- Shared T cell epitopes across GAS M types offer promising targets for multivalent vaccine development.