A prominent role for invariant T cells in the amphibian Xenopus laevis tadpoles

Abstract

Invariant T (iT) cells expressing an invariant or semi-invariant T cell receptor (TCR) repertoire have gained attention in recent years because of their potential as specialized regulators of immune function. These iT cells are typically restricted by nonclassical MHC class I molecules (e.g., CD1d and MR1) and undergo differentiation pathways distinct from conventional T cells. While the benefit of a limited TCR repertoire may appear counterintuitive in regard to the advantage of the diversified repertoire of conventional T cells allowing for exquisite specificity to antigens, the full biological importance and evolutionary conservation of iT cells are just starting to emerge. It is generally considered that iT cells are specialized to recognize conserved antigens equivalent to pathogen-associated molecular pattern. Until recently, little was known about the evolution of iT cells. The identification of class Ib and class I-like genes in nonmammalian vertebrates, despite the heterogeneity and variable numbers of these genes among species, suggests that iT cells are also present in ectothermic vertebrates. Indeed, recent studies in the amphibian Xenopus have revealed a drastic overrepresentation of several invariant TCRs in tadpoles and identified a prominent nonclassical MHC class I-restricted iT cell subset critical for tadpole antiviral immunity. This suggests an important and perhaps even dominant role of multiple nonclassical MHC class I-restricted iT cell populations in tadpoles and, by extension, other aquatic vertebrates with rapid external development that are under pressure to produce a functional lymphocyte repertoire with small numbers of cells.