Molecular analysis of V gene sequences encoding cytotoxic anti-streptococcal/anti-myosin monoclonal antibody 36.2.2 that recognizes the heart cell surface protein laminin.
Anti-streptococcal/anti-myosin mAb 36.2.2 is unique among the cross-reactive anti-streptococcal mAbs due to its cytotoxicity for rat heart cells and its ability to strongly label the surface of heart cells in indirect immunofluorescence assays. In this study, cytotoxic mAb 36.2.2 was found to react strongly with the extracellular matrix protein laminin in immunoblots and inhibition assays, while 11 other cross-reactive anti-streptococcal mAbs did not react with laminin and were not cytotoxic. Cytotoxicity appeared to correlate with the presence of laminin on the surface of cells. Heavy and light chain variable region genes encoding mAb 36.2.2 were highly homologous to other V genes encoding anti-carbohydrate and/or autoantibodies. VH, JH, and Jkappa segments of mAb 36.2.2 may be encoded by germline gene segments. The VH segment may be identical with an as yet unidentified VH7183 family germline sequence, and the 36.2.2 Vkappa region gene is encoded by a Vkappa8 family member.
Antone
S M
SM
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73162, USA.
Adderson
E E
EE
Mertens
N M
NM
Cunningham
M W
MW
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D005803:Genes, Immunoglobulin; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007797:Laminin / Q000276:immunology*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry*; D009218:Myosins / Q000276:immunology*; D051381:Rats; D017422:Sequence Analysis, DNA; D013297:Streptococcus pyogenes / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D007797:Laminin; D009218:Myosins