Two different nonclassical MHC class I-restricted invariant T cell lineages with non-overlapping antiviral and anti-mycobacterial immune functions in the amphibian Xenopus

Abstract

Unconventional T cells, including disparate populations of MHC class Ib-reactive innate T (iT) cells are emerging as key factors in the immune system partly due to their public antigen specificities and rapid effector responses. The biological relevance and evolutionary conservation of iT cells have, over the past few years, been strengthened by studies in the amphibian Xenopus, which have revealed an overrepresentation of several invariant TCRs in tadpoles and identified a prominent subset of iT cells (invariant Vα6 [iVα6]) restricted by the nonclassical MHC class Ib molecule XNC10. Recently, we showed that similar to CD1d restricted iNKT cells in humans and mice Xenopus iVα6 T cells are critical for early antiviral immunity. Here, using RNAi loss-of-function by transgenesis targeting another Xenopus nonclassical gene, XNC4, we have identified a different XNC4-dependent iT cell population expressing one of the 6 previously identified overrepresented TCRα rearrangements (TRAV45 joined to TRAJ1.14). We show that this invariant Vα45 [iVα45] T cell population is critical for antibacterial immunity against Mycobacterium marinum. These data suggest that functionally distinct populations of MHC class Ib-reactive iT cell populations play a prominent role in amphibian immune defense and as such may represent a more primordial immune cell type that previously thought.