The cysteine residues in the cytoplasmic tail of CD8 alpha are required for its coreceptor function.
The cytoplasmic segment of the CD8 alpha polypeptide includes both a cysteine-containing motif that is required for its association with the tyrosine kinase p56lck, and two serine residues which are likely to be phosphorylated and involved in inside-out signaling phenomena. To determine the relative importance of these residues for CD8 function, a mouse T cell hybridoma expressing a T cell receptor specific for the class I major histocompatibility product H-2Kb was transfected with a set of CD8 alpha chain genes encoding polypeptides in which the cytoplasmic cysteine or serine residues were substituted with alanine. When challenged with Kb-transfected L cells, T cell transfectants expressing CD8 alpha beta or CD8 alpha alpha dimers with substituted cytoplasmic serine residues responded nearly as well as wild-type CD8 transfectants. In marked contrast, the CD8 alpha polypeptides bearing substitutions of both cytoplasmic cysteine residues were totally impaired in their ability to complement the co-expressed T cell receptor.
Hoeveler
A
A
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Malissen
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D016827:CD8 Antigens / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry*; D003593:Cytoplasm / Q000648:ultrastructure; D015870:Gene Expression; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D016827:CD8 Antigens; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D003545:Cysteine