NDLI: MMTV superantigens coerce an unconventional topology between the TCR and MHC class II.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shoukry, Naglaa H. Fortin, Jean-Simon Younes, Souheil Gauthier, Catherine Sékaly, Rafick-Pierre Yassine-Diab, Bader Fremont, Daved H. Thibodeau, Jacques Azar, Georges A. Genève, Laetitia
Description	Author Affiliation: Fortin JS ( Laboratoire d'Immunologie Moléculaire, Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec HC3 3J7, Canada)
Abstract	Mouse mammary tumor virus superantigens (vSAGs) are notorious for defying structural characterization, and a consensus has yet to be reached regarding their ability to bridge the TCR to MHC class II (MHCII). In this study, we determined the topology of the T cell signaling complex by examining the respective relation of vSAG7 with the MHCII molecule, MHCII-associated peptide, and TCR. We used covalently linked peptide/MHCII complexes to demonstrate that vSAG presentation is tolerant to variation in the protruding side chains of the peptide, but can be sensitive to the nature of the protruding N-terminal extension. An original approach in which vSAG was covalently linked to either MHCII chain confirmed that vSAG binds outside the peptide binding groove. Also, whereas the C-terminal vSAG segment binds to the MHCII -chain in a conformation-sensitive manner, the membrane-proximal N-terminal domain binds the ß-chain. Because both moieties of the mature vSAG remain noncovalently associated after processing, our results suggest that vSAG crosslinks MHCII molecules. Comparing different T cell hybridomas, we identified key residues on the MHCII -chain that are differentially recognized by the CDR3ß when engaged by vSAG. Finally, we show that the highly conserved tyrosine residue found in the vSAg TGXY motif is required for T cell activation. Our results reveal a novel SAG/MHCII/TCR architecture in which vSAGs coerce a near-canonical docking between MHCII and TCR that allows eschewing of traditional CDR3 binding with the associated peptide in favor of MHCII -chain binding. Our findings highlight the plasticity of the TCR CDRs.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-02-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Viral Immunology Histocompatibility Antigens Class Ii Mammary Tumor Virus, Mouse Receptors, Antigen, T-cell, Alpha-beta Superantigens Binding Sites Hek293 Cells Hela Cells Jurkat Cells Lymphocyte Activation Protein Binding Protein Structure, Tertiary Signal Transduction T-lymphocytes Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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