THE BASIS OF UNEXPECTED CROSS-REACTIONS SHOWN BY HUMAN MONOCLONAL-ANTIBODIES AGAINST BLOOD-GROUP ANTIGENS AS REVEALED BY IMMUNOHISTOCHEMISTRY

Twenty-six of 44 human monoclonal IgM antibodies (MAbs) against erythr ocyte blood group antigens were previously found to display unexpected cross-reactions with tissue components. The aim of the present study was to identify target antigens for these MAbs. Twenty of the 26 tissu e-reactive subset reacted with intermediate filaments (IF) as shown by double-labelling immunofluorescence microscopy with mouse monoclonal antibodies against IF proteins; 14 of these MAbs also bound to purifie d IF proteins in solid-phase radiobinding assays. Four MAbs reacted wi th vimentin or glial fibrillary acidic protein (GFAP), whereas 16 show ed more widespread reactivity with two or more classes of IF. Three MA bs bound to all five classes of IF, namely vimentin, GFAP, desmin, cyt okeratins, and neurofilaments using immunohistochemistry or solid-phas e radiobinding assays. Purified IF proteins were able to inhibit hemag glutination by IF-reactive MAbs. These results show a high incidence o f cross-reactions with IF by a panel of antibodies produced from immun ized donors, which has implications for the interpretation of immunohi stochemical findings using antibodies produced from healthy and diseas ed persons.