The structure of the human allo-ligand HLA-B*3501 in complex with a cytochrome p450 peptide: Steric hindrance influences TCR allo-recognition

Christopher Hourigan, Maria Harkiolaki, Neil A. Peterson, John I. Bell, E. Yvonne Jones, Christopher A. O'Callaghan

Research output: Contribution to journalArticle

Abstract

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:FIRGRAYGL 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 languageEnglish (US)
Pages (from-to)3288-3293
Number of pages6
JournalEuropean Journal of Immunology
Volume36
Issue number12
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

Fingerprint

HLA-B Antigens
Cytochrome P-450 Enzyme System
Ligands
Peptides
Human Herpesvirus 4
T-Lymphocytes
T-Cell Antigen Receptor
Tissue Donors
Viruses

Keywords

  • Allorecognition
  • MHC
  • TCR
  • Transplantation

ASJC Scopus subject areas

  • Immunology

Cite this

The structure of the human allo-ligand HLA-B*3501 in complex with a cytochrome p450 peptide : Steric hindrance influences TCR allo-recognition. / Hourigan, Christopher; Harkiolaki, Maria; Peterson, Neil A.; Bell, John I.; Jones, E. Yvonne; O'Callaghan, Christopher A.

In: European Journal of Immunology, Vol. 36, No. 12, 01.12.2006, p. 3288-3293.

Research output: Contribution to journalArticle

Hourigan, Christopher ; Harkiolaki, Maria ; Peterson, Neil A. ; Bell, John I. ; Jones, E. Yvonne ; O'Callaghan, Christopher A. / The structure of the human allo-ligand HLA-B*3501 in complex with a cytochrome p450 peptide : Steric hindrance influences TCR allo-recognition. In: European Journal of Immunology. 2006 ; Vol. 36, No. 12. pp. 3288-3293.
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