CD94 FUNCTIONS AS A NATURAL-KILLER-CELL INHIBITORY RECEPTOR FOR DIFFERENT HLA CLASS-I ALLELES - IDENTIFICATION OF THE INHIBITORY FORM OF CD94 BY THE USE OF NOVEL MONOCLONAL-ANTIBODIES

CD94 molecules have been suggested to function as inhibitory natural k iller cell (NK) receptors involved in the recognition of HLA-B alleles sharing the Bw6 supertypic specificity. In this study, we show that C D94 molecules may play a more general role: they are also involved in the recognition of other HLA class I molecules, including HLA-C and at least some HLA-A alleles. The inhibitory effect mediated by CD94 mole cules on NK cytolytic activity is lower in magnitude than that of bona fide inhibitory receptors such as p58 or p70. Distinct from the other human NK receptors involved in HLA class I recognition, CD94 is expre ssed on virtually all NK cells. In addition, it has been shown to be f unctionally heterogeneous since, in different clones, CD94 mediated ei ther cell triggering or inhibition. Although NK cells expressing inhib itory CD94 molecules are usually characterized by a CD94(bright) pheno type, there is no precise correlation between fluorescence intensity a nd inhibitory or activating function. Here, we describe two novel mono clonal antibodies (mAb) which selectively recognize inhibitory CD94 mo lecules and bind to a subset (variable in size among different donors) of CD94(bright) cells. The use of these mAb allows the direct assessm ent of NK cells expressing inhibitory CD94 receptors both at the popul ation and at the clonal level.