Participation of CD11a-c/CD18, CD2 and RGD-binding receptors in endogenous and interleukin-2-stimulated NK activity of CD3-negative large granular lymphocytes.
The effect of RGD-sequence-containing pentapeptides and monoclonal antibodies (MAbs) against the adhesion molecules CD11a-c/CD18, ICAM-1 (CD54) and CD2 on the binding and cytotoxicity of endogenous (freshly purified) and IL-2-stimulated CD3-negative NK cells has been studied. Antibody to CD18 exerted the most significant inhibition of adhesion and cytotoxicity of endogenous NK cells to MOLT-4 lymphoma cells, followed by antibodies to CD2 and CD54. Antibodies to either CD11a, CD11b or CD11c did not inhibit adhesion when used separately, whereas as a mixture their inhibitory capacity was as strong as that of anti-CD18. Antibodies against CD18, CD54 and CD2 exerted an additive effect on the inhibition of adhesion. Their combination eradicated the binding of endogenous NK cells. The RGD-containing peptide did not inhibit the binding or cytotoxicity of freshly purified NK cells to MOLT-4, whereas some inhibition was detected against the adenocarcinoma cell line COLO-205. According to FACS analysis, IL-2 increases the expression of CD2 and CD54 on NK cells. However, the relative contribution of the adhesion molecules to the NK cell binding did not change as a result of the stimulation with IL-2. The RGD-peptide substantially inhibited the binding of IL-2-stimulated killer cells to COLO, and the combination of this peptide with MAbs to CD18, CD54 and CD2 practically blocked the adhesion. Our results indicate that both CD11a-c/CD18- (involving the 3 heterodimers) and CD2-dependent adhesion pathways are used by LGL in endogenous and IL-2 stimulated natural killing. In addition, RGD-binding receptors are involved in adhesion to some target cells.
Timonen
T
T
Department of Pathology, University of Helsinki, Finland.
Gahmberg
C G
CG
Patarroyo
M
M
D000937:Antigen-Antibody Reactions / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D018801:CD2 Antigens; D017252:CD3 Complex / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D018000:Receptors, Peptide
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D018821:CD18 Antigens; D018801:CD2 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; D018000:Receptors, Peptide; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor