NDLI: Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation.

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Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Stone, Jennifer D. Kranz, David M. Jones, Lindsay L. Colf, Leremy A. Garcia, K. Christopher
Description	Country affiliation: United States Author Affiliation: Jones LL ( Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.)
Abstract	T cells are known to cross-react with diverse peptide MHC Ags through their alphabeta TCR. To explore the basis of such cross-reactivity, we examined the 2C TCR that recognizes two structurally distinct ligands, SIY-K(b) and alloantigen QL9-L(d). In this study we characterized the cross-reactivity of several high-affinity 2C TCR variants that contained mutations only in the CDR3alpha loop. Two of the TCR lost their ability to cross-react with the reciprocal ligand (SIY-K(b)), whereas another TCR (m67) maintained reactivity with both ligands. Crystal structures of four of the TCRs in complex with QL9-L(d) showed that CDR1, CDR2, and CDR3beta conformations and docking orientations were remarkably similar. Although the CDR3alpha loop of TCR m67 conferred a 2000-fold higher affinity for SIY-K(b), the TCR maintained the same docking angle on QL9-L(d) as the 2C TCR. Thus, CDR3alpha dictated the affinity and level of cross-reactivity, yet it did so without affecting the conserved docking orientation.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Complementarity Determining Regions Chemistry H-2 Antigens Metabolism Oligopeptides Receptors, Antigen, T-cell, Alpha-beta Amino Acid Sequence Animals Genetics Conserved Sequence Cross Reactions Immunology Histocompatibility Antigen H-2d Ketoglutarate Dehydrogenase Complex Mice Molecular Sequence Data Protein Binding Protein Transport Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't 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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Distinct CDR3 Conformations in T Cell Receptors Determine the Level of Cross-Reactivity for Diverse Antigens, but Not the Docking Orientation

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Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation.

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