Subunit Composition of Pre–T Cell Receptor Complexes Expressed by Primary Thymocytes: CD3δ Is Physically Associated but Not Functionally Required |
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| Authors: | Marc A. Berger, Vibhuti Dav , Michele R. Rhodes, Gayle C. Bosma, Melvin J. Bosma, Dietmar J. Kappes, David L. Wiest |
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| Affiliation: | Marc A. Berger, Vibhuti Davé, Michele R. Rhodes, Gayle C. Bosma, Melvin J. Bosma, Dietmar J. Kappes, and David L. Wiest |
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| Abstract: | Maturation of immature CD4−CD8− (DN) thymocytes to the CD4+CD8+ (DP) stage of development is driven by signals transduced through a pre–T cell receptor (TCR) complex, whose hallmark is a novel subunit termed pre-Tα (pTα). However, the precise role of pre-TCRs in mediating the DN to DP transition remains unclear. Moreover, progress in understanding pre-TCR function has been hampered thus far because previous attempts to demonstrate expression of pTα-containing pre-TCRs on the surface of normal thymocytes have been unsuccessful. In this report, we demonstrate for the first time that pTα-containing pre-TCR complexes are expressed at low levels on the surface of primary thymocytes and that these pre-TCR complexes comprise a disulfide-linked pTα–TCR-β heterodimer associated not only with CD3-γ and -ε, as previously reported, but also with ζ and δ. Interestingly, while CD3-δ is associated with the pre-TCR complex, it is not required for pre-TCR function, as evidenced by the generation of normal numbers of DP thymocytes in CD3-δ–deficient mice. The fact that any of the signaling components of the pre-TCR are dispensable for pre-TCR function is indeed surprising, given that few pre-TCR complexes are actually expressed on the surface of primary thymocytes in vivo. Thus, pre-TCRs do not require the full array of TCR-associated signaling subunits (γ, δ, ε, and ζ), possibly because pTα itself possesses signaling capabilities. |
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