Regulation of T-cell functions by MHC class II self-presentation.

The role of MHC class II in the control of T-cell responses to self and foreign antigens is still unclear. No unifying principle yet explains how class II molecules repress immunity to self or allogeneic antigens. Our recent data in a model of tolerance to allogeneic grafts, probably induced by allele-specific class II peptides, suggest that it is by presenting themselves [class II peptide(s) docked on self class II, in a complex we have named T-Lo] that class II controls T-cell activity. The engagement of the regulatory T (T-reg)-cell T-cell receptor (TCR) with self T-Lo would explain the beneficial effect of donor-recipient class II matching in clinical transplantation, the correlation between T-cell suppression and class II, and the altered T-reg-cell functions observed in class II-dependent autoimmune pathologies.