title: Reversed T Cell Receptor Docking on a Major Histocompatibility Class I Complex Limits Involvement in the Immune Response.
abstract: The anti-viral T cell response is drawn from the naive T cell repertoire. During influenza infection, the CD8+T cell response to an H-2Db-restricted nucleoprotein epitope (NP366) is characterized by preferential expansion of T cells bearing TRBV13+T cell receptors (TCRs) and avoidance of TRBV17+T cells, despite the latter dominating the naive precursor repertoire. We found two TRBV17+TCRs that bound H-2Db-NP366with a 180° reversed polarity compared to the canonical TCR-pMHC-I docking. The TRBV17 β-chain dominated the interaction and, whereas the complementarity determining region-3 (CDR3) loops exclusively mediated contacts with the MHC-I, peptide specificity was attributable to germline-encoded recognition. Nevertheless, the TRBV17+TCR exhibited moderate affinity toward H-2Db-NP366and was capable of signal transduction. Thus, the naive CD8+T cell pool can comprise TCRs adopting reversed pMHC-I docking modes that limit their involvement in the immune response.
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Jesseka
authors.initials: J
authors.lastname: Chadderton
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Del Campo
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Carine
authors.initials: C
authors.lastname: Farenc
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Florian
authors.initials: F
authors.lastname: Wiede
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Josephs
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Xavier Y X
authors.initials: XYX
authors.lastname: Sng
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Michiko
authors.initials: M
authors.lastname: Mirams
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Watson
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Tiganis
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Kylie M
authors.initials: KM
authors.lastname: Quinn
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia; Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: jamie.rossjohn@monash.edu.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: nicole.la.gruta@monash.edu.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray / Q000379:methods; D000939:Epitopes / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell
keywords: T cell activation; T cell recruitment; TCR recognition of pMHCI; reversed TCR docking