MHC-restricted T cell receptor signaling is required for alpha beta TCR replacement of the pre T cell receptor

European Journal of Immunology
Andrew L CroxfordThorsten Buch

Abstract

A developmental block is imposed on CD25(+)CD44(-) thymocytes at the beta-selection checkpoint in the absence of the pre T cell receptor (preTCR) alpha-chain, pTalpha. Early surface expression of a transgenic alphabeta TCR has been shown to partially circumvent this block, such that thymocytes progress to the CD4(+)CD8(+) double-positive stage. We wanted to analyze whether a restricting MHC element is required for alphabeta TCR-expressing double-negative (DN) thymocytes to overcome the developmental block in pTalpha-deficient animals. We used the HY-I knock-in model that endows thymocytes with alphabeta TCR expression in the DN compartment but has the advantage of physiological expression levels, in contrast to conventional TCR transgenes. On a pTalpha-deficient background, this HY-I TCR transgene 'rescued' CD25(+)CD44(-) thymocytes from apoptosis and enabled progression to later differentiation stages. On a non-selecting MHC background, however, pTalpha-deficient HY-I mice presented a pronounced reduction in numbers of splenocytes and thymocytes when compared to animals of selecting MHC genotype, showing that MHC restriction is necessary to drive HY-TCR-mediated rescue of pTalpha-deficient thymocytes.

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Citations

Aug 28, 2013·The Journal of Experimental Medicine·Taras KreslavskyHarald von Boehmer
Dec 10, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna L FurmanskiJulian Dyson
Sep 30, 2015·Immunity, Inflammation and Disease·Jessica P Leyva-RangelVianney Ortiz-Navarrete

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