title: Fully functional HLA B27-restricted CD4+ as well as CD8+ T cell responses in TCR transgenic mice.
abstract: The strong association of HLA B27 with spondyloarthropathies contrasts strikingly with most autoimmune diseases, which are HLA class II associated and thought to be mediated by CD4+ T lymphocytes. By introducing a human-derived HLA B27-restricted TCR into HLA B27 transgenic mice, we have obtained a functional TCR transgenic model, GRb, dependent on HLA B27 for response. Surprisingly, HLA B27 supported CD4+ as well as CD8+ T cell responses in vivo and in vitro. Further, HLA B27-restricted CD4+ T cells were capable of differentiation into a range of Th1 and Th2 T cell subsets with normal patterns of cytokine expression. The transgenic T cells were also able to enhance clearance of recombinant vaccinia virus containing influenza nucleoprotein in vivo. This is the first description of a human HLA class I-restricted TCR transgenic line. The existence of CD4+ MHC class I-restricted T cells has significant implications for immune regulation in autoimmunity and, in particular, in HLA B27-associated arthritis. We believe that this model provides a novel system for the study of unusual T cell behavior in vivo.
authors.affiliation: Edward Jenner Institute for Vaccine Research, Compton, Nr. Newbury, Berkshire RG 20 7NN, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Roddis
authors.forename: Robert W
authors.initials: RW
authors.lastname: Carter
authors.forename: Mei-Yi
authors.initials: MY
authors.lastname: Sun
authors.forename: Thomas
authors.initials: T
authors.lastname: Weissensteiner
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Paul
authors.initials: P
authors.lastname: Bowness
authors.forename: Helen C
authors.initials: HC
authors.lastname: Bodmer
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D016601:RNA-Binding Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019076:Transgenes / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology / Q000494:pharmacology
chemical_list: D016207:Cytokines; D015796:HLA-B27 Antigen; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014758:Viral Core Proteins; D007371:Interferon-gamma