Dynamics of CD3gammaepsilon and CD3deltaepsilon dimer expression during murine T cell development.

The preTCR, gammadeltaTCR, and alphabetaTCR 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 dimers (CD3gammaepsilon and CD3deltaepsilon) and TCRzetazeta dimers for their assembly, stable surface expression and signal transduction. Notably, differences have been reported regarding the requirement for CD3delta in the assembly, surface expression and signaling abilities of the three TCR isoforms. Specifically, it has been shown that both the preTCR and gammadeltaTCR do not require CD3delta to transduce signals, whereas the alphabetaTCR does. The differences noted between the murine alphabeta- and gammadeltaTCRs in their requirement for CD3delta can be easily explained by the fact that CD3delta is a component of the alphabetaTCR but not the gammadeltaTCR. However, it is not clear why the preTCR does not require CD3delta, considering that CD3delta 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 CD3deltaepsilon dimer expression is developmentally regulated during early T cell development such that preTCRs expressed on immature CD4(-)CD8(-) thymocytes contain primarily CD3gammaepsilon dimers while those expressed on CD4(+)CD8(+) thymocytes express both CD3deltaepsilon and CD3gammaepsilon dimers. To investigate this, we determined whether the expression of CD3delta and CD3gamma are developmentally regulated and whether there are differences in the availability and/or stability of CD3deltaepsilon and CD3gammaepsilon dimers during early T cell development. We report that even though both CD3delta and CD3gamma were expressed at relatively high levels in immature CD4(-)CD8(-) thymocytes, CD3gammaepsilon dimers predominated over CD3deltaepsilon dimers at this early stage. However, expression of CD3deltaepsilon dimers was rescued when pTalpha, TCRbeta and TCRalpha chains were also expressed at the CD4(-)CD8(-) stage, indicating that the relative amounts of pTalpha, TCRbeta and TCRalpha chains during early thymocyte development control the stability and, therefore, availability of CD3deltaepsilon dimers.