2cik | pdb_00002cik

INSIGHTS INTO CROSSREACTIVITY IN HUMAN ALLORECOGNITION: THE STRUCTURE OF HLA-B35011 PRESENTING AN EPITOPE DERIVED FROM CYTOCHROME P450.

File:2cik.jpg

spinqualitylabelsall models 2cik, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

Overview

Virus-specific T cell populations have been implicated in allo-recognition. The subdominant T cell receptor JL12 recognizes both HLA-B*0801 presenting the Epstein-Barr virus-derived peptide FLRGRAYGL and also HLA-B*3501 presenting the cytochrome p450 self peptide KPIVVLHGY. This cross-reactivity could promote the rejection of HLA-B*3501-positive cells in Epstein-Barr virus-exposed HLA-B*0801 recipients. LC13, the dominant TCR against the HLA-B*0801:FLRGRAYGL complex, fails to recognize HLA-B*3501:KPIVVLHGY. We report the 1.75-Angstrom resolution crystal structure of the human allo-ligand HLA-B*3501:KPIVVLHGY. Similarities between this structure and that of HLA-B*0801:FLRGRAYGL may facilitate cross-recognition by JL12. Moreover, the elevated peptide position in HLA-B*3501:KPIVVLHGY would provide steric hindrance to LC13, preventing it from interacting in the manner in which it interacts with HLA-B*0801:FLRGRAYGL. These findings are relevant to understanding the basis of T cell cross-reactivity in allo-recognition, optimal transplant donor-recipient matching and developing specific molecular inhibitors of allo-recognition.

Disease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]

About this Structure

2CIK is a Protein complex structure of sequences from Homo sapiens with GOL as ligand. Known structural/functional Site: AC1. Full crystallographic information is available from OCA.

Reference

The structure of the human allo-ligand HLA-B*3501 in complex with a cytochrome p450 peptide: steric hindrance influences TCR allo-recognition., Hourigan CS, Harkiolaki M, Peterson NA, Bell JI, Jones EY, O'Callaghan CA, Eur J Immunol. 2006 Dec;36(12):3288-93. PMID:17109469

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