TAP1 super(---) mice present oligoclonal BV-BJ expansions following the rejection of grafts bearing self antigens

• Published in: Immunology 2006-08, Vol.118 (4), p.461-471
• Main Authors: Marrero, Idania, Huffman, Donald, Kalil, Jorge, Sercarz, Eli E, Coelho, Veronica
• Format: Article
• Language: English
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2006.02387.x

Our previous work showed that transporter associated with antigen processing 1 (TAP1) super(---) (H-2 super(b)) mice rejected grafts from H-2 super(b) mice which display a normal density of class I major histocompatibility complex (MHC) molecules at the cell surface. Our results indicated that H-2 super(b) molecules themselves may be a target in this kind of rejection and that CD4 super(+) T cells play a major role in this autoreactive process. Our data also suggested that TAP1 super(---) mice, in addition to the well-recognized phenotype of class I and CD8 super(+) T-cell deficiency, present a functional alteration in their autoreactive CD4 super(+) 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 super(---) mice and transplanted TAP1 super(---) mice that rejected B6 heart grafts or responded to synthetic self H-2K super(b) peptides. Importantly, oligoclonal T-cell expansions shared by different animals were detected in the peripheral T-cell repertoire of transplanted TAP1 super(---) mice. Such public expansions were also induced in vitro by H-2K super(b) 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 super(---) mice.