Dynamics of CD3γɛ and CD3δɛ dimer expression during murine T cell development

Abstract

The preTCR, γδTCR, and αβTCR 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 (CD3γɛ and CD3δɛ) and TCRζζ dimers for their assembly, stable surface expression and signal transduction. Notably, differences have been reported regarding the requirement for CD3δ in the assembly, surface expression and signaling abilities of the three TCR isoforms. Specifically, it has been shown that both the preTCR and γδTCR do not require CD3δ to transduce signals, whereas the αβTCR does. The differences noted between the murine αβ- and γδTCRs in their requirement for CD3δ can be easily explained by the fact that CD3δ is a component of the αβTCR but not the γδTCR. However, it is not clear why the preTCR does not require CD3δ, considering that CD3δ 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 CD3δɛ dimer expression is developmentally regulated during early T cell development such that preTCRs expressed on immature CD4−CD8− thymocytes contain primarily CD3γɛ dimers while those expressed on CD4+CD8+ thymocytes express both CD3δɛ and CD3γɛ dimers. To investigate this, we determined whether the expression of CD3δ and CD3γ are developmentally regulated and whether there are differences in the availability and/or stability of CD3δɛ and CD3γɛ dimers during early T cell development. We report that even though both CD3δ and CD3γ were expressed at relatively high levels in immature CD4−CD8− thymocytes, CD3γɛ dimers predominated over CD3δɛ dimers at this early stage. However, expression of CD3δɛ dimers was rescued when pTα, TCRβ and TCRα chains were also expressed at the CD4−CD8− stage, indicating that the relative amounts of pTα, TCRβ and TCRα chains during early thymocyte development control the stability and, therefore, availability of CD3δɛ dimers.