title: Subunit composition of pre-T cell receptor complexes expressed by primary thymocytes: CD3 delta is physically associated but not functionally required.
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-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, as 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.
authors.affiliation: Division of Basic Sciences, Immunobiology Working Group, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. ma_berger@fccc.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Berger
authors.forename: V
authors.initials: V
authors.lastname: Davé
authors.forename: M R
authors.initials: MR
authors.lastname: Rhodes
authors.forename: G C
authors.initials: GC
authors.lastname: Bosma
authors.forename: M J
authors.initials: MJ
authors.lastname: Bosma
authors.forename: D J
authors.initials: DJ
authors.lastname: Kappes
authors.forename: D L
authors.initials: DL
authors.lastname: Wiest
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D004220:Disulfides; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
chemical_list: D004220:Disulfides; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C061836:antigen T cell receptor, epsilon chain; C054979:antigen T cell receptor, zeta chain