Fig. 2 |. Classification of non-classical T cells on the basis of central or peripheral development.

Unconventional T cells can be broadly separated into three groups largely based on their selection and differentiation patterns and how that affects their acquisition of effector programs. Group I unconventional T cells, which are classified by their acquisition of effector functions in the thymus, include NKT, MAIT and H2-M3-restricted T cells, and DETCs. Uniquely for NKT, MAIT and H2-M3-restricted T cells, this process takes place on double-positive thymocytes and requires the SAP pathway. These cells ultimately seed tissues such as the skin and liver, in which they exert their effector functions. Group II unconventional T cells include BTNL-reactive TCRγδ T cells, which leave the thymus naive and acquire effector functions in the periphery on tissue-specific self-ligands. Finally, group III unconventional T cells follow the conventional T cell path by leaving the thymus naive and only acquire effector functions once they encounter their cognate foreign antigen in the periphery. Grey cells represent naive T cells; different coloured cells represent effector T cells.