Nonclassical MHC class I-dependent invariant T cells are evolutionarily conserved and prominent from early development in amphibians.

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TitleNonclassical MHC class I-dependent invariant T cells are evolutionarily conserved and prominent from early development in amphibians.
Publication TypeJournal Article
Year of Publication2013
AuthorsEdholm, E-S, Saez, L-MAlbertorio, Gill, AL, Gill, SR, Grayfer, L, Haynes, N, Myers, JR, Robert, J
JournalProc Natl Acad Sci U S A
Volume110
Issue35
Pagination14342-7
Date Published2013 Aug 27
ISSN1091-6490
KeywordsHydrogen-Ion Concentration
Abstract

Human and murine MHC nonclassical class Ib-restricted invariant T (iT) cell subsets, such as invariant natural killer T cells (iNKT) and mucosal-associated invariant T cells, have specialized functions early in immune responses, especially in modulating subsequent adaptive immune responses. Here, we characterize a prominent iT population in the amphibian Xenopus laevis and show the requirement of the class Ib molecule, Xenopus nonclassical gene 10, in its differentiation and function. Using Xenopus nonclassical gene 10 tetramers and RNAi loss of function by transgenesis, we identified a large class Ib-dependent CD8(-)/CD4(-) iT subset in unmanipulated frogs and tadpoles. This population is critical for antiviral immunity during early larval stages when classical MHC class Ia function is suboptimal. Furthermore, in young tadpoles with low class Ia expression, deep sequencing revealed additional preponderant invariant T cell receptor (TCR)α rearrangements, implying other iT cell subsets and a predominant selection process mediated by other class Ib molecules. The restriction and requirement of class Ib molecules for development and antiviral immunity of a mammalian iNKT or mucosal-associated invariant T cell counterpart in the amphibian Xenopus show the importance of iT cells in the emergence and evolution of the adaptive immune system.

DOI10.1073/pnas.1309840110
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID23940320
PubMed Central IDPMC3761575
Grant ListR24-AI-059830 / AI / NIAID NIH HHS / United States
R25-GM064133 / GM / NIGMS NIH HHS / United States