SUBUNIT COMPOSITION OF PRE-T CELL-RECEPTOR COMPLEXES EXPRESSED BY PRIMARY THYMOCYTES - CD3-DELTA IS PHYSICALLY ASSOCIATED BUT NOT FUNCTIONALLY REQUIRED

Maturation of immature CD4(-)CD8(-)(DN) thymocytes to the CD4(+)CD8(+) (DP) stage of development is driven by signals transduced through a p re-T cell receptor (TCR) complex, whose hallmark is a novel subunit te rmed pre-T alpha (pT alpha). 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 p revious attempts to demonstrate expression of pT alpha-containing pre- TCRs on the surface of normal thymocytes have been unsuccessful In thi s report, we demonstrate for the first time that pT alpha-containing p re-TCR complexes are expressed at low levels on the surface of primary thymocytes and that these pre-TCR complexes comprise a disulfide-link ed pT alpha-TCR-beta heterodimer associated not only with CD3-gamma an d -epsilon, as previously reported, but also with zeta and delta. Inte restingly, while CD3-delta is associated with the pre-TCR complex, it is not required for pre-TCR function, evidenced by the generation of n ormal numbers of DP thymocytes in CD3-delta-deficient mice. The fact t hat any of the signaling components of the pre-TCR are dispensable for pre-TCR function is indeed surprising, given that few pre-TCR complex es are actually expressed on the surface of primary thymocytes in vivo . Thus, pre-TCRs do not require the full array of TCR-associated signa ling subunits (gamma, delta, epsilon, and zeta), possibly because pT a lpha itself possesses signaling capabilities.