NDLI: Effect of CDR3 sequences and distal V gene residues in regulating TCR-MHC contacts and ligand specificity.

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Effect of CDR3 sequences and distal V gene residues in regulating TCR-MHC contacts and ligand specificity.

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Effect of CDR3 sequences and distal V gene residues in regulating TCR-MHC contacts and ligand specificity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Duke, Brian Li, Guoqi Stern, Lawrence J. Trenh, Peter Huseby, Eric S. Stadinski, Brian D. Huseby, Priya G.
Description	Author Affiliation: Stadinski BD ( Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655); Trenh P ( Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655); Duke B ( Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655); Huseby PG ( Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655); Li G ( Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655); Stern LJ ( Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655); Huseby ES ( Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655)
Abstract	The mature T cell repertoire has the ability to orchestrate immunity to a wide range of potential pathogen challenges. This ability stems from thymic development producing individual T cell clonotypes that express TCRs with unique patterns of Ag reactivity. The Ag specificity of TCRs is created from the combinatorial pairing of one of a set of germline encoded TCR V and Vß gene segments with randomly created CDR3 sequences. How the amalgamation of germline encoded and randomly created TCR sequences results in Ag receptors with unique patterns of ligand specificity is not fully understood. Using cellular, biophysical, and structural analyses, we show that CDR3 residues can modulate the geometry in which TCRs bind peptide-MHC (pMHC), governing whether and how germline encoded TCR V and Vß residues interact with MHC. In addition, a CDR1 residue that is positioned distal to the TCR-pMHC binding interface is shown to contribute to the peptide specificity of T cells. These findings demonstrate that the specificity of individual T cell clonotypes arises not only from TCR residues that create direct contacts with the pMHC, but also from a collection of indirect effects that modulate how TCR residues are used to bind pMHC.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1303209
Journal	The Journal of Immunology
Issue Number	12
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Complementarity Determining Regions Immunology Histocompatibility Antigens Peptides Receptors, Antigen, T-cell, Alpha-beta T-lymphocytes Animals Chemistry Genetics Mice Mice, Knockout Research Support, N.i.h., Extramural Research Support, U.s. Gov't, Non-p.h.s. Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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