Molecular analysis of cross-reactive anti-myosin/anti-streptococcal mouse monoclonal antibodies

Nucleotide sequences of VH- and VL-genes of anti-myosin/anti-streptococcal monoclonal antibodies (mAbs) were analyzed and compared with their highly d etailed antigen binding reactivities. Antigen-specificities of the cross-re active mAbs included myosin, streptococcal M-protein, actin, keratin, N-ace tyl-beta -D-glucosamine, vimentin, DNA, tropomyosin, troponin, and laminin as previously described. After nucleotide sequence analysis, homology indic ated that some of the V gene sequences aligned with antibodies recognizing gangliosides and blood group antigens glycophorin M and N. Therefore, mAb r eactivity with gangliosides and glycophorin M and N was identified. The cro ss-reactive mAbs utilized a heterogeneous group of germline V-heavy genes c omprised of nine J558-, four 7183- and two Q52-family VH-genes. Germline V- light genes utilized by the mAbs included six V kappa4/5-, three V kappa8-, two V kappa 10-, three V kappa 19- and one V kappa 23-family VL-genes. No preferential VH/VL-chains correlated with any of the 12 different antigen r eactivities, even for mAbs with nearly identical cross-reactivities. Howeve r, we did find that the cross-reactive mAb germline genes within a V gene f amily shared more homology among themselves than with other germline genes within their V gene families, suggesting convergent mutation. Cross-reactiv e mAbs with the highest relative avidity for myosin were found in the VH718 3 family which contained two cytotoxic mAbs. Antibodies with V gene sequenc es most homologous to those of our cross-reactive anti-myosin/anti-streptoc occal mAbs had specificities for laminin, DNA, carbohydrates, or blood grou p antigens and were reported to cause autoimmune disease in mice. (C) 2001 Elsevier Science Ltd. All rights reserved.