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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.","bibjson":{"author":[{"initials":"CS","lastname":"Hourigan","name":"Hourigan CS"},{"initials":"M","lastname":"Harkiolaki","name":"Harkiolaki M"},{"initials":"NA","lastname":"Peterson","name":"Peterson NA"},{"initials":"JI","lastname":"Bell","name":"Bell JI"},{"initials":"EY","lastname":"Jones","name":"Jones EY"},{"initials":"CA","lastname":"O'Callaghan","name":"O'Callaghan CA"}],"identifier":[{"id":"10.1002/eji.200636234","type":"doi"},{"id":"17109469","type":"pubmed"}],"issue":["12"],"journal":{"iso_abbreviation":"Eur. J. 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