| First Author | Marrero I | Year | 2006 |
| Journal | Immunology | Volume | 118 |
| Issue | 4 | Pages | 461-71 |
| PubMed ID | 16895555 | Mgi Jnum | J:114445 |
| Mgi Id | MGI:3689129 | Doi | 10.1111/j.1365-2567.2006.02387.x |
| Citation | Marrero I, et al. (2006) TAP1-/- mice present oligoclonal BV-BJ expansions following the rejection of grafts bearing self antigens. Immunology 118(4):461-71 |
| abstractText | 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 naive 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. |
