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Berger MA , Dave V , Rhodes MR , Bosma GC , Bosma MJ , Kappes DJ , Wiest DL
Subunit composition of pre-T cell receptor complexes expressed by primary thymocytes: CD3 delta is physically associated but not functionally required
Journal of Experimental Medicine. 1997 Nov 3;186(9) :1461-1467
AbstractMaturation 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 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 previous attempts to demonstrate expression of pT alpha-containing pre- TCRs on the surface of normal thymocytes have been unsuccessful In this report, we demonstrate for the first time that pT alpha-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 alpha-TCR-beta heterodimer associated not only with CD3-gamma and -epsilon, as previously reported, but also with zeta and delta. Interestingly, while CD3-delta is associated with the pre-TCR complex, it is not required for pre-TCR function, evidenced by the generation of normal numbers of DP thymocytes in CD3-delta- 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 (gamma, delta, epsilon, and zeta), possibly because pT alpha itself possesses signaling capabilities.
NotesTimes Cited: 48 English Article YE942 J EXP MED