Role of nonpolymorphic MHC-I and innate T cells in Xenopus larval resistance and tolerigenic immunity to mycobacteria    

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B1041
Abstract ID: 5521

Presenting Author:
Martin Pavelka , Professor at UR Med., Martin Pavelka

Abstract:

To date the amphibian Xenopus is the only species outside mice and human where nonpolymorphic MHC-Ib molecules directing the development and function of innate (i)T cells with limited TCR repertoire has been characterized. Xenopus tadpoles provides a unique comparative model for investigating the roles of iT cells. Unlike mammals tadpoles rely mostly on a few distinct prominent iT cell subsets interacting with cognate nonpolymorphic MHC-Ib (XNC) molecules that confer resistance to pathogens such as mycobacteria. Here, we is investigated the iT cell subset iVα45 (expressing the invariant TCRα rearrangement Vα545-Jα1.14) and its cognate MHC-Ib XNC4 in response to Mycobacterium marinum (Mm) by reverse genetics and proliferation assays. Loss-of-function obtained by RNA silencing and CRISPR/Cas9 mutagenesis of XNC4 or iVα45 T cells dramatically impaired tadpole resistance to Mm. Furthermore, iT cell proliferative response against Mm was very limited in tadpoles compared to adults, which contrasted with the rapid iVa45 T cell recruitment from the spleen to infection sites detected by qPCR and flow cytometry using XNC4-tetramers. In contrast, tadpole iT cells showed a high proliferative rate upon PHA stimulation in vitro but exhibited a lower TCR signaling amplitude than adult frog T cells. These data suggest that similar to mammalian neonatal T cells, tadpole T cells are functionally distinct from adult counterparts.