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 detailed antigen binding reactivities. Antigen-specificities of the cross-reactive mAbs included myosin, streptococcal M-protein, actin, keratin, N-acetyl-beta-D-glucosamine, vimentin, DNA, tropomyosin, troponin, and laminin as previously described. After nucleotide sequence analysis, homology indicated that some of the V gene sequences aligned with antibodies recognizing gangliosides and blood group antigens glycophorin M and N. Therefore, mAb reactivity with gangliosides and glycophorin M and N was identified. The cross-reactive mAbs utilized a heterogeneous group of germline V-heavy genes comprised of nine J558-, four 7183- and two Q52-family VH-genes. Germline V-light genes utilized by the mAbs included six Vkappa4/5-, three Vkappa8-, two Vkappa10-, three Vkappa19- and one Vkappa23-family VL-genes. No preferential VH/VL-chains correlated with any of the 12 different antigen reactivities, even for mAbs with nearly identical cross-reactivities. However, we did find that the cross-reactive mAb germline genes within a V gene family shared more homology among themselves than with other germline genes within their V gene families, suggesting convergent mutation. Cross-reactive mAbs with the highest relative avidity for myosin were found in the VH7183 family which contained two cytotoxic mAbs. Antibodies with V gene sequences most homologous to those of our cross-reactive anti-myosin/anti-streptococcal mAbs had specificities for laminin, DNA, carbohydrates, or blood group antigens and were reported to cause autoimmune disease in mice.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Biomedical Research Center, 975 N.E. 10th Street, Oklahoma City, OK 73104, USA.
N M
NM
Mertens
J E
JE
Galvin
E E
EE
Adderson
M W
MW
Cunningham
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics*; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D000915:Antibody Affinity; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000276:immunology*; D003429:Cross Reactions; D018076:DNA, Complementary; D020868:Gene Silencing; D005854:Germ Cells; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009218:Myosins / Q000276:immunology*; D013291:Streptococcus / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; C014689:streptococcal M protein; D009218:Myosins