Oddball T cells

Although we typically think of T cells as expressing variant T-cell receptors (TCRs) that engage the classical MHC class I or II molecules, several other T-cell subsets exist, which are rather more odd in nature. For example, natural killer T (NKT) cells express an invariant Vα14 TCRα chain and are restricted by the MHC-like molecule CD1d. Other T cells that express invariant receptors are the human Vα7.2-Jα33 and mouse Vα19-Jα33 cells. A recent study now shows that these T cells preferentially localize in the gut and are restricted by an MHC class-I-like molecule known as MR1.

Initial studies showed that hVα7.2-Jα33 and mVα19-Jα33 T cells are enriched in the lamina propria region of the gut. These mucosal-associated T (MAIT) cells were more abundant in mice that lack the transporter for antigen processing (TAP) or invariant chain (in which the number of classical T cells is low because of the reduced expression of MHC class I and II molecules), but absent in mice that lack β₂-microglobulin (β₂m), indicating that β₂m is required for selection.

To determine which cell type mediates the selection of these cells, various bone-marrow chimaeras were generated. These showed that β₂m-positive B cells were necessary for the selection of the MAIT cells. The MHC class-I-related molecule MR1 seemed to be a possible candidate ligand for MAIT cells. MR1 transfectants could stimulate cytokine release from MAIT cells and this interaction was inhibited using antibodies specific for the TCR. MR1-deficient mice had essentially no Vα19-Jα33-positive T cells. Furthermore, germ-free mice lacked MAIT cells, indicating that their selection is dependent on the presence of commensal gut flora.

The authors speculate that these MAIT cells are important for the regulation of immune responses at mucosal surfaces.