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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Published on: February 28, 2019

Molecular requirements for MHC class II alpha-chain engagement and allelic discrimination by the bacterial

Katherine J Kasper1, Wang Xi, A K M Nur-Ur Rahman

  • 1Department of Microbiology and Immunology, University of Western Ontario, Canada.

Journal of Immunology (Baltimore, Md. : 1950)
|August 21, 2008
PubMed

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.

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