2B4 is constitutively associated with linker for the activation of T cells in glycolipid-enriched microdomains: properties required for 2B4 lytic function.
2B4 is a receptor belonging to the Ig superfamily and is found on all murine NK cells as well as a small subset of T cells. Previous studies have found that cross-linking of the 2B4 receptor results in both increased cytotoxicity and IFN-gamma secretion. We have discovered that 2B4 from transfected NK and T cell lines, as well as from primary murine cells, coimmunoprecipitates with the phosphoprotein linker for the activation of T cells (LAT), which is essential for TCR-mediated signaling. This association is independent of both 2B4 phosphorylation and the cytoplasmic tail of 2B4. We have found that, along with LAT, 2B4 is constitutively located in glycolipid-enriched microdomains of the plasma membrane. In fact, 2B4 appears to associate with LAT only when it localizes to glycolipid-enriched microdomains. This localization of 2B4 occurs due to a CxC cysteine motif found in the transmembrane region, as determined by mutagenesis studies. 2B4-mediated cytotoxicity is defective in the absence of LAT, indicating that LAT is a required intermediate for 2B4 signal transduction. However, we have also shown that LAT association alone is not sufficient for maximal 2B4 activation.
Klem
Jennifer
J
Department of Pathology and Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9072, USA.
Verrett
Pamela C
PC
Kumar
Vinay
V
Schatzle
John D
JD
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D021962:Membrane Microdomains / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000071176:Signaling Lymphocytic Activation Molecule Family; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C084093:CD244 protein, human; D002352:Carrier Proteins; C490007:Cd244a protein, mouse; D006017:Glycolipids; C110810:LAT protein, human; C491734:Lat protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family