Clonal variation in expression of a human melanoma antigen defined by a monoclonal antibody.

Previous work established 3 monoclonal mouse antibodies, 3.1, 3.2, and 3.3, which define an antigenic determinant that is expressed by a human melanoma, M1804, and, in smaller amounts, by another melanoma, M1801. In the present study we first investigated the expression of this determinant, which we refer to as 3.1, by cells from different melanomas, using membrane immunofluorescence techniques. We found that some tumors, such as M1801, appeared to be mixtures of cells that varied in their expression of 3.1. Clones were established from cultures of M1801 and M1804, and their expression of 3.1 was studied by a variety of serologic techniques, including membrane immunofluorescence, complement-dependent cytotoxicity, and absorption. Some of the clones expressed determinant 3.1, and others did not. By recloning a late passage of a 3.1-positive clone from M1801, a negative subclone was established, proving that 3.1-positive cells can yield 3.1-negative progeny. A clone that had lost 3.1 was tested and found to still express p97, an antigen defined by a different monoclonal antibody. We conclude that since some melanomas are heterogeneous with respect to the expression of antigenic determinant 3.1, and since 3.1 negative progeny can be derived from 3.1-positive cells, there is the potential for selection of 3.1-negative cells. The implications of this, for antigenic determinant 3.1 and possibly for other tumor antigens, must be taken into account when considering using monoclonal antibodies for tumor therapy.