title: Functional ambivalence of the Kp43 (CD94) NK cell-associated surface antigen.
abstract: We originally characterized the Kp43 (CD94) surface Ag, whose expression is restricted to human NK cells and a minor T lymphocyte subset. As shown in the present study, anti-Kp43 mAbs but not their F(ab')2 fragments markedly inhibited the cytolytic activity of polyclonal-activated NK cells in a redirected lysis assay against the murine P815 cell line. Furthermore, anti-Kp43 mAbs also down-regulated the CD16-dependent redirected killing and PHA-induced lectin-dependent cellular cytotoxicity. However, the intensity of the inhibitory effect was variable and no significant down-regulation of cytotoxicity was substantiated in NK cell populations from some individuals. A similar variability in the responsiveness to anti-Kp43 mAb was noticed when fresh CD3- lymphocyte populations were tested: in some donors we observed the induction of redirected lysis, whereas in other samples the Kp43-specific mAb inhibited cytotoxicity. The analysis of single cell-derived microcultures provided a clue to interpret the variable responsiveness of polyclonal cell populations; remarkably, the cytolytic activity of some NK clones was inhibited, whereas that of others was either stimulated or unaffected. The pattern of responsiveness in the cytolytic assay correlated with TNF production upon stimulation with solid phase-bound anti-Kp43 mAbs. The different types of clones could be derived from the same individual, although their relative proportions varied from donor to donor. Moreover, Kp43 appeared to be coupled differently to signal transduction pathways, because (Ca2+)i mobilization in the presence of the Kp43-specific mAbs was substantiated only in clones that were activated in the redirected lysis assay.
authors.affiliation: Immunology Service, La Princesa Hospital, Autonomous University of Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Pérez-Villar
authors.forename: I
authors.initials: I
authors.lastname: Melero
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Carretero
authors.forename: J
authors.initials: J
authors.lastname: Aramburu
authors.forename: S
authors.initials: S
authors.lastname: Sivori
authors.forename: A M
authors.initials: AM
authors.lastname: Orengo
authors.forename: A
authors.initials: A
authors.lastname: Moretta
authors.forename: M
authors.initials: M
authors.lastname: López-Botet
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium