title: Clonotypically similar hybrid αβ T cell receptors can exhibit markedly different surface expression, antigen specificity and cross-reactivity.
abstract: Emerging data indicate that particular major histocompatibility complex (MHC)-bound antigenic peptides can be recognized by identical or near-identical αβ T cell receptors (TCRs) in different individuals. To establish the functional relevance of this phenomenon, we artificially paired α and β chains from closely related TCRs specific for the human leucocyte antigen (HLA)-B*35:01-restricted HIV-1 negative regulatory factor (Nef)-derived epitope VY8 (VPLRPMTY, residues 74-81). Several hybrid TCRs generated in this manner failed to express at the cell surface, despite near homology with naturally isolated αβ chain combinations. Moreover, a substantial proportion of those αβ TCRs that did express lost specificity for the index VY8 peptide sequence. One such hybrid αβ pair gained neo-variant specificity in the context of the VY8 backbone. Collectively, these data show that clonotypically similar TCRs can display profound differences in surface expression, antigen specificity and cross-reactivity with potential relevance for the control of mutable viruses.
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.|Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: C
authors.initials: C
authors.lastname: Motozono
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Bridgeman
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Sewell
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.|International Research Center for Medical Research, Kumamoto University, Kumamoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ueno
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003429:Cross Reactions / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015870:Gene Expression; D050939:Gene Fusion; D055786:Gene Knockout Techniques; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054311:nef Gene Products, Human Immunodeficiency Virus
keywords: CD8+ T cells; CDR3; HIV; TCR