Molecular requirements for MHC class II alpha-chain engagement and allelic discrimination by the bacterial superantigen streptococcal pyrogenic exotoxin C.
Superantigens (SAgs) are microbial toxins that bind to both TCR beta-chain variable domains (Vbetas) and MHC class II molecules, resulting in the activation of T cells in a Vbeta-specific manner. It is now well established that different isoforms of MHC II molecules can play a significant role in the immune response to bacterial SAgs. In this work, using directed mutational studies in conjunction with functional analyses, we provide a complete functional map of the low-affinity MHC II alpha-chain binding interface of the SAg streptococcal pyrogenic exotoxin C (SpeC) and identify a functional epitope in the beta-barrel domain that is required for the activation of T cells. Using cell lines that exclusively express individual MHC II isoforms, our studies provide a molecular basis for the selectivity of SpeC-MHC II recognition, and provide one mechanism by how SAgs are capable of distinguishing between different MHC II alleles.
Kasper
Katherine J
KJ
Department of Microbiology and Immunology, University of Western Ontario, Canada.
Xi
Wang
W
Rahman
A K M Nur-Ur
AK
Nooh
Mohammed M
MM
Kotb
Malak
M
Sundberg
Eric J
EJ
Madrenas
Joaquín
J
McCormick
John K
JK
D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005098:Exotoxins / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D054730:Protein Interaction Domains and Motifs / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D001426:Bacterial Proteins; D000939:Epitopes; D005098:Exotoxins; D000949:Histocompatibility Antigens Class II; C027951:erythrogenic toxin