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Notes: Summary This manuscript reviews recent studies on the characterization of functional surface antigens on human NK cells. A series of cloned NK cell lines has been utilized for examination of these structures. These clones provide a relatively large number of cells with a stable phenotype and consistent specific cytotoxicity, which reflect the diversity of uncultured NK cells in normal peripheral blood. Almost all clones express the T11 antigen, some have a mature T-cell phenotype (T3+, T11+), and only one (JT1) does not reveal any T-cell antigen at all (T3−, T11+). Using NK clones to generate monoclonal antibodies specific for NK-associated antigens, two structures have been identified, NKH1 and NKH2. NKH1 appears to be exclusively expressed on large granular lymphocytes (LGL) of peripheral blood and was found to be a pan-NK cell antigen. NKH2 is also expressed primarily by LGL, but NKH2-positive LGL do not display a high level of NK activity. Another surface structure that has been found to play an important role in NK cell function is the T11 antigen/E rosette receptor complex, which is expressed in 80% of peripheral blood NK cells. The T11 antigen complex has been described as possessing the T111, T112, and T113 antigens and is an important alternate pathway for antigen-independent T-cell activation. Using anti-T112 and anti-T113 monoclonal antibodies, IL-2 receptor expression could be induced on various NK clones if they expressed the correct T11 antigenic epitope. As anti-T112/3 antibodies had a direct proliferative effect on NK cells with mature T-cell phenotype (T3+), it is proposed that the production of IL-2 by NK clones is largely dependent on the T-cell phenotype of NK cells. All NK clones expressed IL-2 receptor at low density and therefore needed a ten fold higher concentration for maximal proliferation than T-cell clones. For some T-cell-like NK clones, the T3 antigen complex and a T-cell receptor-like structure, NKTa or NKTb, have been shown to define the target cell specificity. The activation antigen, TNKTAR, was characterized as the recognition structure on the target cell for these NK cells. For both T3− and T3+ NK clones, the LFA-1 antigen has been shown to play an important role in effector/target cell interaction. As previously described for CTL, the LFA-1 molecule is involved in NK cytotoxicity as a nonspecific adhesion-strengthening molecule at the effector cell level. In summary, NK cells have been found to have a number of unique surface antigens such as NKH1 and NKH2, which can be used to identify and characterize NK cells in vivo. In addition, analysis of surface antigens on NK cells has identified a number of functional structures, such as T11, T3, NKTa and LFA-1, which are shared by T-cells and which function in a fashion similar to both types of cells. Taken together, this analysis therefore indicates that NK cells have a strong functional relationship with T-cells and supports the conclusion that these cells are derived from the T-cell lineage.