Biochemical association of CD45 with the T cell receptor complex: regulation by CD45 isoform and during T cell activation.
CD45 is the predominant transmembrane tyrosine phosphatase in lymphocytes and is required for the efficient induction of T cell receptor signaling and activation. However, the regulation of CD45 activity and substrate specificity are poorly understood. In the present study, we demonstrate a basal biochemical association of CD45 with the T cell receptor complex that is regulated in part by CD45 isoform expression. Further, maintenance of CD45/TCR association is differentially regulated following TCR ligation with peptide: a partial agonist peptide induces CD45/TCR dissociation while an agonist peptide promotes sustained association in a CD4-dependent manner. These data suggest that T cell receptor signaling pathways may be modulated by altering access of CD45 to TCR-associated substrates involved in T cell activation.
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D003593:Cytoplasm; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D020033:Protein Isoforms / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008024:Ligands; D010455:Peptides; D020033:Protein Isoforms; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens