EVOLUTIONARY CONSERVATION OF A HUMAN FUNCTION-ASSOCIATED MOLECULE ON MURINE NATURAL-KILLER-CELLS - EXPRESSION AND FUNCTION

Using a novel anti-natural killer (NK) cell monoclonal antibody (Moab) , we have recently identified an evolutionary conserved function-assoc iated molecule (FAM) present on fish, rat and human NK cells. This mol ecule is involved in NK cell function as anti-FAM MoAbs inhibit cytoto xicity, stimulate lymphokine secretion and inhibit conjugate formation between effector cells and target cells. We now have examined murine NK cells for the presence of this structure. It was observed by two-co lour flow cytometric analysis that the anti-FAM MoAb 5C6 specifically bound to a subpopulation of nylon wool non-adherent splenic lymphocyte s (19-20%). The expression of the FAM molecule was restricted to NK ce lls that expressed the NK1.1 antigen. Neither T cells, B cells, nor ma crophages reacted with the anti-FAM MoAb. Analysis of FAM expression i n various lymphoid tissues revealed that splenocytes expressed the gre atest numbers of MoAb(+) cells. Generation of lymphokine-activated kil ler (LAK) cells and adherent lymphokine-activated killer (ALAK) cells resulted in higher levels of FAM expression. The anti-FAM MoAb 5C6 als o detected the presence of FAM on fresh SCID NK cells. It was demonstr ated that the anti-FAM MoAb 5C6 inhibited the lysis of target cells by endogenous NK cells, activated NK cells, 5d LAK cells, ALAK cells and SCID NK cells. Moreover, conjugate assays demonstrated involvement of this molecule in recognition between NK cells and target cells.