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

Andrew L. Croxford, Özlem Akilli-Ozturk, Frederic Rieux-Laucat, Irmgard Förster, Ari Waisman, Thorsten Buch

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


A developmental block is imposed on CD25+CD44- thymocytes at the β-selection checkpoint in the absence of the pre T cell receptor (preTCR) α-chain, pTa. Early surface expression of a transgenic αβ 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 αβ TCR-expressing double-negative (DN) thymocytes to overcome the developmental block in pTα-deficient animals. We used the HY-I knock-in model that endows thymocytes with αβ TCR expression in the DN compartment but has the advantage of physiological expression levels, in contrast to conventional TCR transgenes. On a pTα-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, pTα-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 pTα-deficient thymocytes.

Original languageEnglish
Pages (from-to)391-399
Number of pages9
JournalEuropean Journal of Immunology
Issue number2
StatePublished - Feb 2008
Externally publishedYes


  • MHC restriction
  • Pre T cell receptor
  • T cell development


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