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Subunit Composition of Pre–T Cell Receptor Complexes Expressed by Primary Thymocytes: CD3 Is Physically Associated but Not Functionally Required

From the Division of Basic Sciences, Immunobiology Working Group, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

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-T (pT). 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 pT-containing pre-TCRs on the surface of normal thymocytes have been unsuccessful. In this report, we demonstrate for the first time that pT-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 pT–TCR-β heterodimer associated not only with CD3- and -, as previously reported, but also with and . Interestingly, while CD3- 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-–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 (, , , and ), possibly because pT itself possesses signaling capabilities.

¹ Abbreviations used in this paper: 2D NRxR, two-dimensional nonreducing x reducing; CD3-⁰, CD3-–deficient; DN, CD4^–CD8^– double negative; DP, CD4⁺CD8⁺ double positive; HRP-Av, horseradish peroxidase–conjugated streptavindin; pT, pre-T; pT–β, pT–TCR-β; TCR-⁰, TCR-–deficient.

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