Richard a . Houghten , James G . Karras , John H . Vaughan , and Dennis

The molecular basis of immunoglobulin idiotypes (1) has been pursued in several well-defined antibody systems (2-7). The accumulated results have suggested that the hypervariable regions (complementarity-determining regions, CDR) 1 of the light and heavy polypeptide chains usually contribute to the formation of idiotypic determinants. In the extensively analyzed murine antidextran model, one private idiotype and one public idiotype (cross-reactive idiotypes, CRI) were assigned, respectively to the third and the second hypervariable regions of the heavy chain (6). In most other cases, idiotypic determinants have not been associated definitively with a specific amino acid sequence (2). The latter result is not surprising, considering that antiidiotype antibodies elicited by immunization with intact immunoglobulin often recognize determinants dependent upon a particular quaternary interaction of the light and heavy chains (2). Using carefully absorbed rabbit antisera, Kunkel and colleagues (8) first described the unusual existence of two major CRI (Wa and Po) among human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RF) from unrelated individuals with cryogiobulinemia. The larger Wa group includes ~60% of monoional IgM-RF (8, 9). Amino acid sequence analysis of the variable regions of two Wa-CRI positive IgM-RF (Sie and Wol) has revealed a marked homology between the kappa light chains, but not the heavy chains (10). However, the precise chemical nature of the Wa-CRI has remained unclear. To clarify these issues, we generated a murine monoclonal antibody (mAb 17109) that recognized a CRI shared by the Wa-CRI positive IgM-RF Sie and Glo but not by the Wa-CRI negative IgM-RF Lay and Pom (1 1). Although made This work was supported by National Institutes of Health grants AM 25443, AM 21175, and AG04100. P. P. Chen is a postdoctoral Fellow of the Arthritis Foundation. This is publication no. 3360BCR from the Research Institute of Scripps Clinic, La Jolla, CA. 1 Abbreviations used in this paper: BBS, borate-buffered saline; BSA, bovine serum albumin; CDR, complementarity-determining regions; CRI, cross-reactive idiotypes; ELISA, enzyme-linked immunosorbent assay; KLH, keyhole limpet hemocyanin; mAb, monoclonal antibody; PBS, phosphatebuffered saline; PSH3, synthetic peptide corresponding to the 3rd CDR of the heavy chain of the IgMRF Sie; PSL2, synthetic peptide corresponding to the 2nd CDR and adjacent residues on the light chain of the IgM-RF Sie; RF, rheumatoid factors.