Anti-ergotypic immunoregulation

T-cell vaccination (TCV) controls pathogenic autoimmune T-cell responses via two different regulatory cell populations: anti-idiotypic and anti-ergotypic T cells. Anti-idiotypic T cells recognize clone-specific determinants, like the CDR3 region of the T-cell receptor. Anti-ergotypic T cells recognize antigenic determinants derived from activation markers, which are upregulated by activated T cells, like CD25. In this review, we analyse the different components of the anti-ergotypic response: (1) the target T cells, which can be CD8+ or CD4+ T cells that express TCRalphabeta or TCRgammadelta; (2) the ergotope, which can be a T cell-restricted ergotope not expressed by other cell types or a widely expressed, shared ergotope and (3) the anti-ergotypic T cells, which are detectable in the naive immune system, but whose numbers can be expanded during the induction of an immune response against, or as a result of TCV or specific, anti-ergotypic vaccination. Finally, we discuss possible interactions between anti-ergotypic regulators and other regulatory T cells. We propose that the expression of major histocompatibility complex class II molecules by regulatory CD4+CD25+ T cells may make possible the cross-regulation of anti-ergotypic and CD4+CD25+ regulatory T cells, fine-tuning immunoregulation in the mature immune system.