STRUCTURAL CHARACTERISTICS OF 4 HUMAN HYBRIDOMA ANTIBODIES SPECIFIC FOR THE PP65 PROTEIN OF THE HUMAN CYTOMEGALOVIRUS AND THEIR RELATIONSHIP TO HUMAN RHEUMATOID FACTORS

Four human hybridoma antibodies directed against the human cytomegalov irus (CMV) were characterized with respect to their immunoglobulin gen e usage and expression of rheumatoid factor (RF) associated idiotypes and variable region epitopes. The aims of these experiments were: (I) to characterize the immunoglobulin gene usage of four antibodies direc ted against a single protein of a human pathogen; and (2) to examine h ow this humoral response may be linked to the production of RFs, autoa ntibodies found in the majority of patients with rheumatoid arthritis (RA). All four anti-CMV antibodies were of the gamma heavy chain isoty pe and were specific for the immunodominant 65 kDa viral matrix phosph oprotein (pp65). The four anti-pp65 antibodies expressed different lig ht (L) and heavy (H) chain variable region gene combinations. These we re: V(lambda)1/V(H)3, V(lambda)1/V(H)3, V(lambda)1/V(H)4 and V(lambda) 3/V(H)3, respectively for the HCV-2, HCV-3, HCV-63 and HCV-65 hybridom a cell lines. Although none had RF activity, each of these antibodies expressed a unique set of RF-associated determinants, implying differe nt three-dimensional configurations of the variable regions of these a ntibodies. The HCV-2 antibody, however, had the most extensive similar ities to human RFs since it not only expressed the greatest number of RF-associated determinants but also had a protein sequence that was ve ry homologous to RFs of the ''Po'' idiotypic family. Furthermore, pred icted germline gene usage by anti-CMV antibodies and RFs suggest that some are encoded by identical or similar genes and that the different specificities are achieved by somatic mutations in the L and H chain c omplementarity determining regions (CDRs) and genetic diversity in the H chain CDR3.