Croxford, Andrew L; Akilli-Ozturk, Ozlem; Rieux-Laucat, Frederic; Förster, Irmgard; Waisman, Ari; Buch, Thorsten (2008). MHC-restricted T cell receptor signaling is required for alpha beta TCR replacement of the pre T cell receptor. European Journal of Immunology, 38(2):391-399.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||19 Jun 2012 16:48|
|Last Modified:||27 Nov 2013 22:59|
|Citations:||Web of Science®. Times Cited: 3|
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