CD45 regulates signal transduction and lymphocyte activation by specific association with receptor molecules on T or B cells.
Evidence is presented that the leukocyte common antigen CD45 can regulate both signal transduction by lymphocyte receptor molecules and T- and B-cell proliferation in a manner dependent on specific interactions between these receptors on the cell surface. Formation of homoaggregates of CD3, CD2, or CD28 on the surface of T cells induced by crosslinking with monoclonal antibodies (mAbs) results in an increase in cytoplasmic free calcium concentration ([Ca2+]i). This increase in [Ca2+]i was abolished when these receptors were crosslinked to CD45 on the cell surface. In contrast, the increase in [Ca2+]i induced by formation of homoaggregates of CD4 was strongly amplified when CD4 was coupled to CD45. T-cell proliferation initiated by immobilized anti-CD3 was inhibited by anti-CD45 or anti-CD45R when immobilized on the same surface, but not when in solution. Similarly, proliferation after stimulation of the CD2 and CD28 receptors was inhibited when a CD45 mAb was crosslinked to either CD2 or CD28 mAbs, but not when a CD45-specific mAb was bound to the cell surface separately. In B cells, the increase in [Ca2+]i and resulting proliferation induced by crosslinking either the CD19 or Bgp95 receptors was inhibited by coupling these molecules to CD45. Thus, CD45 appears to modify other cellular receptors functionally when brought into close physical association with them. The homology of the CD45 conserved cytoplasmic domains with a major human placental protein tyrosine phosphatase suggests that the effects of CD45 described here result from alterations in the phosphorylation state of tyrosyl residues in membrane-associated proteins.
Ledbetter
J A
JA
Oncogen Corporation, Seattle, WA 98121.
Tonks
N K
NK
Fischer
E H
EH
Clark
E A
EA
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D004261:DNA Replication; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D006649:Histocompatibility Antigens; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens