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Proc Natl Acad Sci U S A. August 27, 2013; 110 (35): 14342-7.

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

Edholm ES , Albertorio Saez LM , Gill AL , Gill SR , Grayfer L , Haynes N , Myers JR , Robert J .

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.

PubMed ID: 23940320
PMC ID: PMC3761575
Article link: Proc Natl Acad Sci U S A.
Grant support: R24-AI-059830 NIAID NIH HHS , R25-GM064133 NIGMS NIH HHS , R24 AI059830 NIAID NIH HHS , R25 GM064133 NIGMS NIH HHS , R24-AI-059830 NIAID NIH HHS , R25-GM064133 NIGMS NIH HHS

Genes referenced: cyp26a1 myh4 myh6 tnfrsf10b

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