Potential role of major histocompatibility complex class II peptides in regulatory tolerance to vascularized grafts

The inactivation of persisting T lymphocytes reactive to self- and non-self-antigens is a major arm of operational immune tolerance in mammals. Silencing of such T cells proceeds mostly by means of suppression, a process that is mediated by regulatory T-cell subsets and especially by CD4(+)CD(25high) regulatory T cells (Treg). Although Treg activation and ensuing suppressive activity appear to be major histocompatibility complex class II dependent, the fine specificity of Treg T-cell receptors has not yet been elucidated. Recent data from the author's laboratory on a class II gene therapy induction of tolerance to allogeneic kidney grafts suggest that class II peptides are involved as generic signals for Treg activation. A brief compilation of results that would support this hypothesis is discussed in the present article.