Restricting nonclassical MHC genes coevolve with TRAV genes used by innate-like T cells in mammals

Significance

The conservation and cross-reactivity between species of the T-cell receptor (TR)-V regions and restricting major histocompatibility (MH) molecules characterizing innate-like T cells, natural killer T (NKT) and mucosal-associated invariant T (MAIT), indicate important functions for these cells. Yet, we show that the two MAIT-specific genes, TRAV1 and MR1 , have been lost at least three times during the evolution of mammals. In the rabbit, which has few NKT cells and no MR1, we found a candidate invariant TR-α (iTRA) chain and another mammalian MH1Like molecule that seem to coevolve in mammals. Thus, at least three iTRA/MH-like systems were selected during mammalian evolution. The new MH1Like molecule may present a distinct set of antigens to a new innate-like T-cell subset. This study emphasizes the coevolution of TR and MH molecules.