Journal
IMMUNOLOGICAL REVIEWS
Volume 298, Issue 1, Pages 218-236Publisher
WILEY
DOI: 10.1111/imr.12919
Keywords
antigen presentation; BTN2; BTN3; butyrophilin; evolution; gamma delta TCR
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Funding
- German Research Foundation (DFG, Deutsche Forschungsgemeinschaft) [DFG-He 2346-7/1, DFG-He 2346-8/1]
- Wilhelm-Sander-Stiftung [2013.907.2]
- Deutsche Krebshilfe [70112079]
- DFG [RA 3077/1-1]
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Both, jawless and jawed vertebrates possess three lymphocyte lineages defined by highly diverse antigen receptors: Two T-cell- and one B-cell-like lineage. In both phylogenetic groups, the theoretically possible number of individual antigen receptor specificities can even outnumber that of lymphocytes of a whole organism. Despite fundamental differences in structure and genetics of these antigen receptors, convergent evolution led to functional similarities between the lineages. Jawed vertebrates possess alpha beta and gamma delta T-cells defined by eponymous alpha beta and gamma delta T-cell antigen receptors (TCRs). Conventional alpha beta T-cells recognize complexes of Major Histocompatibility Complex (MHC) class I and II molecules and peptides. Non-conventional T-cells, which can be alpha beta or gamma delta T-cells, recognize a large variety of ligands and differ strongly in phenotype and function between species and within an organism. This review describes similarities and differences of non-conventional T-cells of various species and discusses ligands and functions of their TCRs. A special focus is laid on V gamma 9V delta 2 T-cells whose TCRs act as sensors for phosphorylated isoprenoid metabolites, so-called phosphoantigens (PAg), associated with microbial infections or altered host metabolism in cancer or after drug treatment. We discuss the role of butyrophilin (BTN)3A and BTN2A1 in PAg-sensing and how species comparison can help in a better understanding of this human V gamma 9V delta 2 T-cell subset.
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