A monoclonal anti-HLA antibody recognizes a mouse tumor-associated antigen

The monoclonal antibody W6/32.1 recognizes a public determinant on the HLA-A, B and C antigens of all tested human haplotypes. Though the antibody does not bind to normal mouse cells of any H-2 haplotype, it does show an unexpected specificity for the T cell leukemia line MBL-2 from a C57BL/6 mouse. It is shown that the murine antigen recognized by W6/32.1 is on an H-2-like molecule which also carries the determinant recognized by the monoclonal antibody B22-249 R1, specific for the H-2Db antigen. Unlike B22-249 R1, however, W6/32.1 does not bind to normal H-2b lymphocytes, nor to a variety of tumor cell lines of the H-2b haplotype. This cross-reaction is specific to W6/32.1, and is not shared by other monoclonal antibodies of similar anti-HLA specificities. Moreover, the affinity of W6/32.1 for its human antigen is substantially higher than for its mouse antigen. We conclude that W6/32.1 fortuitously recognizes a novel determinant on the H-2Db antigen of MBL-2, rather than an extensive region of structural homology shared between HLA and H-2. Thus for cells of the H-2b allotype this determinant is detected only on MBL-2, and by definition is thus an example of a tumor-associated antigen.