MHC CLASS I LIKE RESTRICTED INNATE-LIKE T CELL LINEAGES WITH ANTI-MYCOBACTERIAL IMMUNE FUNCTIONS IN THE AMPHIBIAN XENOPUS
Eva-Stina Edholm, University of Rochester Medical Center
Eva-Stina Edholm1, Rhoo, Kun Hyoe1 and Jacques Robert1
University of Rochester Medical Center, Department of Microbiology and Immunology, Rochester NY, USA
The biological relevance and evolutionary conservation of innate-like T (iT) cells have been strengthened by their discovery in the amphibian Xenopus where the tadpole T cell receptor repertoire (TCR) is dominated by six overrepresented invariant TCRα rearrangements indicative of 6 iT cell subset. We have previously identified one of these iT cell subset expressing the invariant Vα6Jα1.43 rearrangemnet that is restricted by the MHC class I-like molecule XNC10. Similar to CD1d restricted iNKT cells in humans and mice, iVα6 T cells in Xenopus are critical for early antiviral immune responses. Here, using a combination of RNAi loss-of-function by transgenesis targeting another Xenopus MHC class I-like gene, XNC4, we have identified a new distinct XNC4-dependent iT cell subset expressing one of the other 6 previously identified overrepresented iTCRs (TRAV45 joined to TRAJ1.14). Using XNC4 tetramers and adapting the CRISPR/Cas9-mediated gene editing technique to specifically disrupt the TRAJ1.14 segment thereby effectively ablating the iVα45 rearrangement, we show that this iVα45 T cell subset is not involved in antiviral immune response but is rather critical for immune response against Mycobacterium marinum. These data suggest that different iT cell lineages, restricted by distinct MHC class I-like molecules with functional specialization toward pathogens, play a prominent role in amphibian immune defense and as such may represent a more primordial immune cell type than previously thought.