Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target cells enhances adhesion of resting NK cells.
The beta2 integrin LFA-1 (CD11a/CD18) mediates adhesion of lymphocytes to cells expressing ICAM. The strength of this adhesion is regulated by different signals delivered by cytokines and chemokines, and by the TCR in the case of T cells. To determine the receptor-ligand interactions required for adhesion of resting NK cells, Drosophila cells expressing different combinations of ligands of human NK cell receptors were generated. Expression of ICAM-1 alone was sufficient for an adhesion of resting NK cells that was sensitive to inhibitors of src family kinase and of phosphatidylinositol 3-kinase. Binding of resting NK cells to solid-phase ICAM-1 showed similar signaling requirements. A pulse of either IL-2 or IL-15 to resting NK cells resulted in strongly enhanced, actin-dependent adhesion to insect cells expressing ICAM-1 alone. Coexpression of either LFA-3 (CD58) or CD48 with ICAM-1 resulted in strong adhesion by resting NK cells, even in the absence of cytokines. Therefore, receptors for LFA-3 and CD48 on resting NK cells strengthen the adhesion mediated by LFA-1.
Barber
Domingo F
DF
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852-1727, USA.
Long
Eric O
EO
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000502:physiology; D000071178:CD48 Antigen; D018968:CD58 Antigens / Q000096:biosynthesis* / Q000502:physiology; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D004331:Drosophila melanogaster; D004357:Drug Synergism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007399:Interphase / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D018968:CD58 Antigens; D019409:Interleukin-15; D007376:Interleukin-2; D018799:Intercellular Adhesion Molecule-1