title: T cell allorecognition via molecular mimicry.
abstract: T cells often alloreact with foreign human leukocyte antigens (HLA). Here we showed the LC13 T cell receptor (TCR), selected for recognition on self-HLA-B( *)0801 bound to a viral peptide, alloreacts with B44 allotypes (HLA-B( *)4402 and HLA-B( *)4405) bound to two different allopeptides. Despite extensive polymorphism between HLA-B( *)0801, HLA-B( *)4402, and HLA-B( *)4405 and the disparate sequences of the viral and allopeptides, the LC13 TCR engaged these peptide-HLA (pHLA) complexes identically, accommodating mimicry of the viral peptide by the allopeptide. The viral and allopeptides adopted similar conformations only after TCR ligation, revealing an induced-fit mechanism of molecular mimicry. The LC13 T cells did not alloreact against HLA-B( *)4403, and the single residue polymorphism between HLA-B( *)4402 and HLA-B( *)4403 affected the plasticity of the allopeptide, revealing that molecular mimicry was associated with TCR specificity. Accordingly, molecular mimicry that is HLA and peptide dependent is a mechanism for human T cell alloreactivity between disparate cognate and allogeneic pHLA complexes.
authors.affiliation: The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Whitney A
authors.initials: WA
authors.lastname: Macdonald
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Chen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Julia K
authors.initials: JK
authors.lastname: Archbold
authors.forename: Fleur E
authors.initials: FE
authors.lastname: Tynan
authors.forename: Craig S
authors.initials: CS
authors.lastname: Clements
authors.forename: Mandvi
authors.initials: M
authors.lastname: Bharadwaj
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Philippa M
authors.initials: PM
authors.lastname: Saunders
authors.forename: Matthew C J
authors.initials: MC
authors.lastname: Wilce
authors.forename: Fran
authors.initials: F
authors.lastname: Crawford
authors.forename: Brian
authors.initials: B
authors.lastname: Stadinsky
authors.forename: David
authors.initials: D
authors.lastname: Jackson
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burrows
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
mesh_terms: D002460:Cell Line; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D015795:HLA-B8 Antigen; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D018716:Molecular Mimicry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
chemical_list: C508151:EBNA-3A antigen; D019309:Epstein-Barr Virus Nuclear Antigens; D015235:HLA-B Antigens; C509422:HLA-B*08:01 antigen; D015795:HLA-B8 Antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell