1wbx

From Proteopedia

Revision as of 12:55, 20 March 2008

CRYSTAL STRUCTURES OF MURINE MHC CLASS I H-2 DB AND KB MOLECULES IN COMPLEX WITH CTL EPITOPES FROM INFLUENZA A VIRUS: IMPLICATIONS FOR TCR REPERTOIRE SELECTION AND IMMUNODOMINANCE

Overview

Cytotoxic T lymphocyte (CTL) responses against influenza A virus in C57BL/6 mice are dominated by a small number of viral peptides among many that are capable of binding to major histocompatibility complex (MHC) class I molecules. The basis of this limited immune recognition is unknown. Here, we present X-ray structures of MHC class I molecules in complex with two immunodominant epitopes (PA(224-233)/D(b) and PB1(703-711)/K(b)) and one non-immunogenic epitope (HA(468-477)/D(b)) of the influenza A virus. The immunodominant peptides are each characterized by a bulge at the C terminus, lifting P6 and P7 residues out of the MHC groove, presenting featured structural elements to T-cell receptors (TCRs). Immune recognition of PA(224-233)/D(b) will focus largely on the exposed P7 arginine residue. In contrast, the non-immunogenic HA(468-477) peptide lacks prominent features in this C-terminal bulge. In the K(b)-bound PB1(703-711) epitope, the bulge results from a non-canonical binding motif, such that the mode of presentation of this peptide strongly resembles that of D(b)-bound peptides. Given that PA(224-233)/D(b), PB1(703-711)/K(b) and the previously defined NP(366-374)/D(b) epitopes dominate the primary response to influenza A virus in C57BL/6 mice, our findings indicate that residues of the C-terminal bulge are important in selection of the immunodominant CTL repertoire.

About this Structure

1WBX is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

Reference

Crystal structures of murine MHC Class I H-2 D(b) and K(b) molecules in complex with CTL epitopes from influenza A virus: implications for TCR repertoire selection and immunodominance., Meijers R, Lai CC, Yang Y, Liu JH, Zhong W, Wang JH, Reinherz EL, J Mol Biol. 2005 Feb 4;345(5):1099-110. Epub 2004 Dec 8. PMID:15644207

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