Molecular Requirements for MHC Class II {alpha}-Chain Engagement and Allelic Discrimination by the Bacterial Superantigen Streptococcal Pyrogenic Exotoxin C

Authors

Katherine J. Kasper, University of Western OntarioFollow
Wang Xi, University of Western Ontario
A. K. M. Nur-Ur Rahman, University of Western Ontario
Mohammed M. Nooh, University of Tennessee
Malak Kotb, University of Tennessee
Eric J. Sundberg, Boston Biomedical Research Institute
Joaquín Madrenas, University of Western OntarioFollow
John K. McCormick, University of Western OntarioFollow

Document Type

Article

Publication Date

9-1-2008

Journal

The Journal of Immunology

Volume

181

Issue

5

First Page

3384

Last Page

3392

Abstract

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.