2vlk

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Template:STRUCTURE 2vlk

THE STRUCTURAL DYNAMICS AND ENERGETICS OF AN IMMUNODOMINANT T-CELL RECEPTOR ARE PROGRAMMED BY ITS VBETA DOMAIN

Overview

Immunodominant and public T cell receptor (TCR) usage is relatively common in many viral diseases yet surprising in the context of the large naive TCR repertoire. We examined the highly conserved Vbeta17:Valpha10.2 JM22 T cell response to the influenza matrix peptide (58-66)-HLA-A( *)0201 (HLA-A2-flu) through extensive kinetic, thermodynamic, and structural analyses. We found several conformational adjustments that accompany JM22-HLA-A2-flu binding and identified a binding "hotspot" within the Vbeta domain of the TCR. Within this hotspot, key germline-encoded CDR1 and CDR2 loop residues and a crucial but commonly coded residue in the hypervariable region of CDR3 provide the basis for the substantial bias in the selection of the germline-encoded Vbeta17 domain. The chances of having a substantial number of T cells in the naive repertoire that have HLA-A2-flu-specific Vbeta17 receptors may consequently be relatively high, thus explaining the immunodominant usage of this clonotype.

About this Structure

2VLK is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain., Ishizuka J, Stewart-Jones GB, van der Merwe A, Bell JI, McMichael AJ, Jones EY, Immunity. 2008 Feb;28(2):171-82. PMID:18275829 Page seeded by OCA on Sun May 4 18:59:39 2008