title: TAP1-/- mice present oligoclonal BV-BJ expansions following the rejection of grafts bearing self antigens.
abstract: Our previous work showed that transporter associated with antigen processing 1 (TAP1)-/- (H-2b) mice rejected grafts from H-2b mice which display a normal density of class I major histocompatibility complex (MHC) molecules at the cell surface. Our results indicated that H-2b molecules themselves may be a target in this kind of rejection and that CD4+ T cells play a major role in this autoreactive process. Our data also suggested that TAP1-/- mice, in addition to the well-recognized phenotype of class I and CD8+ T-cell deficiency, present a functional alteration in their autoreactive CD4+ T-cell repertoires. In this model of inflammatory autoreactivity to modified self, we have analysed T-cell receptor (TCR) V-beta-J-beta (BV-BJ) usage by complementarity determining region 3 (CDR3) length spectratyping in splenocytes from naïve TAP1-/- mice and transplanted TAP1-/- mice that rejected B6 heart grafts or responded to synthetic self H-2Kb peptides. Importantly, oligoclonal T-cell expansions shared by different animals were detected in the peripheral T-cell repertoire of transplanted TAP1-/- mice. Such public expansions were also induced in vitro by H-2Kb peptides, suggesting that dominant class I peptides can induce preferential expansions of restricted T-cell populations during rejection. Some of these public T-cell expansions were also detected in transplanted mice even before in vitro stimulation with peptides, indicating that post-transplantation expansion of these populations had occurred in vivo. The functional activity of these T-cell populations awaits elucidation, as do the underlying mechanisms involved in the inflammatory autoreactive process, in TAP1-/- mice.
authors.affiliation: Immunology Laboratory, Heart Institute (InCor), São Paulo University School of Medicine, São Paulo, Brazil.
authors.forename: Idania
authors.initials: I
authors.lastname: Marrero
authors.forename: Donald
authors.initials: D
authors.lastname: Huffman
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Eli E
authors.initials: EE
authors.lastname: Sercarz
authors.forename: Verônica
authors.initials: V
authors.lastname: Coelho
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D022801:Complementarity Determining Regions / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D016027:Heart Transplantation; D017404:In Situ Hybridization, Fluorescence; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D001324:Autoantigens; D022801:Complementarity Determining Regions; D006183:H-2 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; C486171:Tap1 protein, mouse