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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.

Original publication

DOI

10.1002/eji.200636234

Type

Journal article

Journal

Eur J Immunol

Publication Date

12/2006

Volume

36

Pages

3288 - 3293

Keywords

Amino Acid Sequence, Crystallography, X-Ray, Cytochrome P-450 Enzyme System, HLA-B Antigens, HLA-B35 Antigen, Humans, Isoantigens, Ligands, Molecular Sequence Data, Peptide Fragments, Protein Binding, Protein Structure, Tertiary, Receptors, Antigen, T-Cell, alpha-beta, Stereoisomerism