Heterogeneous expression of melanocytic antigens occurs frequently in melanomas and represents a potent barrier to immunotherapy. We previously showed that coordinated losses of several melanocytic antigens are generally attributable to down-regulation of antigen gene expression rather than irreversible mutation.

We have probed the structure of the C4 and V3 domains of human immunodeficiency virus type 1 gpl20 by immunochemical techniques. Monoclonal antibodies (MAbs) recognizing an exposed gpl20 sequence, (E/ K)VGKAAMYAPP, in C4 were differentially sensitive to denaturation of gpl20, implying a conformational component to some of the epitopes. The MAbs recognizing conformation-sensitive C4 structures failed to bind to a gpl20 mutant with an alteration in the sequence of the V3 loop, and their binding to gpl20 was inhibited by both V3 and C4 MAbs. This implies an interaction between the V3 and C4 regions of gpl20, which is supported by the observation that the binding of some MAbs to the V3 loop was often enhanced by amino acid changes in and around the C4 region.