Abstract
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 αβ and γδ T-cells defined by eponymous αβ and γδ T-cell antigen receptors (TCRs). "Conventional" αβ T-cells recognize complexes of Major Histocompatibility Complex (MHC) class I and II molecules and peptides. Non-conventional T-cells, which can be αβ or γδ 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 Vγ9Vδ2 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 Vγ9Vδ2 T-cell subset.
Highlights
The discovery that butyrophilins (BTNs) control the development and activity of human and mouse γδ T-cell subsets,[1,2,3] the increasing knowledge on γδ T-cell antigen receptor (TCR)-ligand interaction[4,5] together with the exploding interest in cell-based therapeutics stimulated a general interest in γδ T-cells during the last years.[6]
We found some cross-reactivity of mAb 103.2 and 20.1 to BTN3-negative cells transduced with vpBTN3 and of WTH-5 with BTN3A1 transductants but neither the inhibitory mAbs 103.2 nor WTH-5 showed cross-species reactivity on primary cells
As discussed in greater detail elsewhere,[102] our murine reporter cell system allows to overcome this obstacle. Using these lines as reporter cells and various human Chr:6-containing cell lines as presenters, we showed that in addition to BTN3A1, other gene(s) on human Chr:[6] are mandatory for hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP)- and Zoledronate- but not for mAb 20.1-induced stimulation.[135]
Summary
A glance over the fence: Using phylogeny and species comparison for a better understanding of antigen recognition by human γδ T-cells.
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