AbstractThe 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 B22‐249R1, specific for the H‐2Dbantigen. Unlike B22‐249R1, however, W6/32.1 does not bind to normal H‐2blymphocytes, nor to a variety of tumor cell lines of the H‐2bhaplotype. This crossreaction 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‐2Dbantigen of MBL‐2, rather than an extensive region of structural homology shared between HLA and H‐2. Thus for cells of the H‐2ballotype this determinant is detected only on MBL‐2, and by definition is thus an exampl