Multiple mutations in the variable region of the kappa light chains of three monoclonal human IgM with anti-myelin-associated glycoprotein activity.
Human monoclonal IgM having an antibody activity directed to myelin-associated glycoprotein have distinctive features. Amino-terminal sequence of light and heavy chains from 6 IgM kappa that we have previously studied indicated that heavy chains belong to the VHIII subgroup, whereas light chains belong to 3 different subgroups of variability (V kappa I 2, V kappa II 1, and V kappa IV 3). We report here the complete sequence of the variable domain of 3 L chains: 2 V kappa IV and 1 V kappa II subgroups. Strikingly an unusually high degree of mutations clustered in the complementarity-determining regions (CDR) 1 and CDR 3 was found and the variable regions were joined to three different JK segments. Amino acid substitutions did not yield similar sequence in the CDRs suggesting that the kappa chains had no predominant role in the unique binding activity of these IgM or alternatively they are directed against different epitopes. Data are consistent with the previously reported lack of easily demonstrated public idiotopes common to anti-myelin-associated glycoprotein IgM. The pathogenesis of these IgM autoantibodies is most likely different from that of previously studied monoclonal rheumatoid factors or cold agglutinins where a genetic restriction of L or H chains or both has been observed.
Mihaesco
E
E
Laboratory of Immunochemistry and Immunopathology, Institut National de la Santé et de la Recherche Médicale U 108, Hôpital Saint-Louis, Paris, France.
Ayadi
H
H
Congy
N
N
Gendron
M C
MC
Roy
J P
JP
Heyermann
H
H
Frangione
B
B
Brouet
J C
JC
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000235:genetics*; D003488:Cyanogen Bromide; D000939:Epitopes / Q000032:analysis; D005803:Genes, Immunoglobulin; D006801:Humans; D007128:Immunoglobulin Fragments / Q000302:isolation & purification; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009185:Myelin Proteins / Q000276:immunology*; D018992:Myelin-Associated Glycoprotein; D014357:Trypsin
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007128:Immunoglobulin Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D014357:Trypsin; D003488:Cyanogen Bromide