Characterization of a conserved helper-T-cell epitope from group A Streptococcal M proteins

Abstract

We have previously defined major histocompatibility complex (MHC) class II-restricted T-cell epitopes from the carboxy-terminal region of group A streptococcal type 5 M protein. In this report, T-cell responses to one of these epitopes have been characterized in detail. T-cell clones from recombinant M5-immunized mice and popliteal lymph node cells from peptide-immunized mice were used to show that sM5[300-3191 is recognized in the context of I-A alleles of four of nine independent MHC class II haplotypes: I-Ad, I-Af, I-Ak, and I-AS. This epitope was also recognized by both helper (Th2) and inflammatory (Thl) subsets of murine T cells. The I-Ad-restricted epitope recognized by BALB/c mice was mapped to the 12-amino-acid peptide sM5[308-3191 and was shown to provide helper function for an immunoglobulin G anti-peptide antibody response in BALB/c mice. Anti-peptide antibody was shown to be specific for M5[304-3151 but failed to recognize intact rM5, suggesting that the conformation of the epitope differed between peptide and protein. However, the results demonstrate that overlapping epitopes can be the focus for both immunoglobulin G antibodies and the T cells which augment their production. Comparison of the available sequences for M proteins indicated that the T-cell epitope within M5[300-319] was highly conserved between M types and hence may elicit helper function for protective antibody responses to a wide range of M types. T-cell epitopes from conserved regions of M proteins which are recognized in the context of multiple MHC haplotypes have potential for the design of multivalent streptococcal vaccines.

Increased β‐haemolytic group A streptococcal M6 serotype and streptodornase B‐specific cellular immune responses in Swedish narcolepsy cases

“…Secondly, streptococcal infection may be associated with superantigen production favouring expansion of certain TCR families associated with autoimmune responses [68]. Some, [69,70], but not all studies addressing anti-M directed T-cell responses [71,72] have suggested that the M protein itself may act as a superantigen preferentially expanding TCR Vb2, 4 and 8 subsets. The present findings show that the M6 or streptodornase B-directed T-cell responses are antigen specific based on T-cell reactivity against synthetic peptides.…”

Regulation of peptide presentation by major histocompatibility complex class II molecules at the surface of macrophages

“…The following synthetic peptides bearing CD4 T cell epitopes were used in this study: (1) 15 EALDKYELENHDLKTK-NEG 33 containing epitope M5 [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] (underlined); (2) 300 DAS-REAKKQVEKALEEANSK 319 covering epitope M5 308-319 (underlined) mapped previously [43,44]; (3) p381-394, 381 LIQEMLKTMESINQ 394 containing epitope SipC 381-394 /A d of the SipC protein of Salmonella typhimurium [45]. All peptides were synthesized by the Molecular Biology Unit, University of Newcastle upon Tyne.…”

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

“…It was demonstrated that T cell clones against the carboxyterminal epitope 300-319, which has been shown to provide helper function for T-dependent IgG responses [12] , recognized peptides processed from M5, M6 and M12, but not M49, streptococci. Our results indicate that T cells against the conserved region of M5 can cross-react with other serotypes of streptococci.…”