Dynamics of CD3γε and CD3δε dimer expression during murine T cell development

The preTCR, gamma delta TCR, and alpha beta TCR are the three isoforms of the T cell antigen receptor that are expressed during thymocyte development. Signaling by these isoforms is required at different stages of T cell development for lineage commitment, thymocyte maturation, and repertoire selection. All three isoforms are multimeric complexes, which are dependent on invariant CD3 dinners (CD3 gamma epsilon and CD3 delta epsilon) and TCR zeta zeta dinners for their assembly, stable surface expression and signal transduction. Notably, differences have been reported regarding the requirement for CD3 delta in the assembly, surface expression and signaling abilities of the three TCR isoforms. Specifically. it has been shown that both the preTCR and gamma delta TCR do not require CD3 delta to transduce signals, whereas the alpha beta TCR does. The differences noted between the murine alpha beta-and gamma delta TCRs in their requirement for CD3 delta can be easily explained by the fact that CD3 delta is a component of the alpha beta TCR but not the gamma delta TCR. However, it is not clear why the preTCR does not require CD3 delta, considering that CD3 delta has been reported to be a subunit of the preTCR. Because the preTCR can be expressed on thymocytes at the immature CD4(-)CD8(-) stage and, to a lesser extent, at the later CD4(+)CD8(+) stage, it is conceivable that CD3 delta epsilon dimer expression is developmentally regulated during early T cell development such that preTCRs expressed on immature CD4(-)CD8(-) thymocytes contain primarily CD3 gamma epsilon dimers while those expressed on CD4(+)CD8(+) thymocytes express both CD3 delta epsilon and CD3 gamma epsilon dinners. To investigate this, we determined whether the expression of CD3 delta and CD3 gamma are developmentally regulated and whether there are differences in the availability and/or stability of CD3 delta epsilon and CD3 gamma epsilon dimers during early T cell development. We report that even though both CD3 delta and CD3 gamma were expressed at relatively high levels in immature CD4(-)CD8(-) thymocytes, CD3 gamma epsilon dimers predominated over CD3 delta epsilon dimers at this early stage. However, expression of CD3 delta epsilon dimers was rescued when pT alpha, TCR beta and TCR alpha chains were also expressed at the CD4(-)CD8(-) stage, indicating that the relative amounts of pT alpha, TCR beta and TCR alpha chains during early thymocyte development control the stability and, therefore, availability of CD3 delta epsilon dimers. (C) 2009 Elsevier Ltd. All rights reserved.