title: CD3 delta establishes a functional link between the T cell receptor and CD8.
abstract: T cells expressing T cell receptor (TCR) complexes that lack CD3 delta, either due to deletion of the CD3 delta gene, or by replacement of the connecting peptide of the TCR alpha chain, exhibit severely impaired positive selection and TCR-mediated activation of CD8 single-positive T cells. Because the same defects have been observed in mice expressing no CD8 beta or tailless CD8 beta, we examined whether CD3 delta serves to couple TCR.CD3 with CD8. To this end we used T cell hybridomas and transgenic mice expressing the T1 TCR, which recognizes a photoreactive derivative of the PbCS 252-260 peptide in the context of H-2K(d). We report that, in thymocytes and hybridomas expressing the T1 TCR.CD3 complex, CD8 alpha beta associates with the TCR. This association was not observed on T1 hybridomas expressing only CD8 alpha alpha or a CD3 delta(-) variant of the T1 TCR. CD3 delta was selectively co-immunoprecipitated with anti-CD8 antibodies, indicating an avid association of CD8 with CD3 delta. Because CD8 alpha beta is a raft constituent, due to this association a fraction of TCR.CD3 is raft-associated. Cross-linking of these TCR-CD8 adducts results in extensive TCR aggregate formation and intracellular calcium mobilization. Thus, CD3 delta couples TCR.CD3 with raft-associated CD8, which is required for effective activation and positive selection of CD8(+) T cells.
authors.affiliation: Institute for Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Doucey
authors.forename: Laurence
authors.initials: L
authors.lastname: Goffin
authors.forename: Dieter
authors.initials: D
authors.lastname: Naeher
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.forename: Petra
authors.initials: P
authors.lastname: Baumgärtner
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Ed
authors.initials: E
authors.lastname: Palmer
authors.forename: Immanuel F
authors.initials: IF
authors.lastname: Luescher
mesh_terms: D000345:Affinity Labels; D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D020013:Calcium Signaling / Q000502:physiology*; D014644:Genetic Variation; D006825:Hybridomas / Q000382:microbiology; D008213:Lymphocyte Activation; D012515:Mast-Cell Sarcoma; D021962:Membrane Microdomains / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011487:Protein Conformation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000345:Affinity Labels; D017252:CD3 Complex; C472562:CD3delta antigen; D016827:CD8 Antigens; D010446:Peptide Fragments; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell