title: The shaping of T cell receptor recognition by self-tolerance.
abstract: During selection of the T cell repertoire, the immune system navigates the subtle distinction between self-restriction and self-tolerance, yet how this is achieved is unclear. Here we describe how self-tolerance toward a trans-HLA (human leukocyte antigen) allotype shapes T cell receptor (TCR) recognition of an Epstein-Barr virus (EBV) determinant (FLRGRAYGL). The recognition of HLA-B8-FLRGRAYGL by two archetypal TCRs was compared. One was a publicly selected TCR, LC13, that is alloreactive with HLA-B44; the other, CF34, lacks HLA-B44 reactivity because it arises when HLA-B44 is coinherited in trans with HLA-B8. Whereas the alloreactive LC13 TCR docked at the C terminus of HLA-B8-FLRGRAYGL, the CF34 TCR docked at the N terminus of HLA-B8-FLRGRAYGL, which coincided with a polymorphic region between HLA-B8 and HLA-B44. The markedly contrasting footprints of the LC13 and CF34 TCRs provided a portrait of how self-tolerance shapes the specificity of TCRs selected into the immune repertoire.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Protein Crystallography Unit, Monash University, Clayton, Victoria, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burrows
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Craig S
authors.initials: CS
authors.lastname: Clements
authors.forename: Yu Chih
authors.initials: YC
authors.lastname: Liu
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Sullivan
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Bell
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
mesh_terms: D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D018360:Crystallography, X-Ray; D015795:HLA-B8 Antigen / Q000737:chemistry / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D020836:Protein Structure, Quaternary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*; D040681:Structural Homology, Protein; D020349:Surface Plasmon Resonance
chemical_list: D000956:Antigens, Viral; D015795:HLA-B8 Antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell