Specificity Revisited

Abstract

Hybridomas and their resultant monclonal antibodies have provided us with powerful tools with which to probe the molecular structure of a wide variety of cells from diverse species. Since the topic of our Workshop is human leucocyte differentiation antigens, this editorial will discuss examples of monoclonal antibodies elicited to these types of human cell antigens. It is clear that in many cases specificity has had to be redefined in molecular terms, because of monoclonal antibodies. Cross-reacitivity, as it used to be defined using polyclonal antibodies to heterogeneous antigens, is no longer a meaningful term. Now, individual epitopes rather than antigens are the basic substrates. Thus, similar antigens may express different epitopes which can be discriminated by the use of different monoclonal antibodies. In addition, antigens which appear to be the same, by virtue of their reactivity with the same monoclonal antibody, may in fact only have an epitope in common. Our laboratory has so far had two clear examples of hybridomas defining different specific epitopes on the same molecule. One is a monoclonal antibody from our laboratory and the Workshop T cell panel. This antibody, designated as DU-SKW3-1 [1, 2], reacts with the 65 000- to 67 000-dalton T cell antigen defined by the monoclonals 17F12 (Leu-1), T101, or 10.2. Although blocking and lysostripping studies showed that monoclonals 17F12 and DU-SKW3-1 detected the same molecule, the first indication that a different epitope was being detected came from leukemic cell phenotyping studies where an occasional T-ALL or CLL cell would react with one or the other of the monoclonals but not both.

This work was supported by grants AM 08054, CA 08975, CA 11265 and CA 15525 from the National Institutes of Health