Mouse monoclonal antibody bearing a VH framework region determinant similar to a rabbit VHa1 allotope

A monoclonal antibody (mAb 6B8.2) was derived from a mouse immunized with rabbit anti-a1 VH allotype antibody. 6B8.2 specifically reacts with a subpopulation (19-44%) of anti-a1 antibodies from each of 17 a1-immunized rabbits, but does not react with normal rabbit Ig or rabbit antibody to other rabbit allotypes. 6B8.2 also reacts with guinea-pig anti-a1 antibodies and a mouse anti-a1 mAb. Surprisingly, 6B8.2 does not represent an anti-idiotype antibody but rather appears to express an 'a1-like' epitope in the VH framework region of the molecule. This conclusion is supported by Western blot analysis and immunoelectron microscopy of 6B8.2 in complex with rabbit anti-a1 antibody. These data reveal that the determinant recognized by anti-a1 antibody is localized to the H-chain and is not at the distal tip of the mAb. Thus, the location of the 'a1-like' determinant of 6B8.2 appears similar, if not identical, to the location of the a1 determinant on Ig molecules from rabbit and goat, suggesting that a framework region a1-like determinant may be widespread and thus evolutionarily conserved in mammals.