Sequence similarities and cross-idiotypic specificity of L chains among human monoclonal IgM kappa with anti-gamma-globulin activity.
The complete amino acid sequence of five light chain variable (V) regions of human monoclonal IgM kappa rheumatoid factors (RF) was determined, and their cross-reactive idiotypes (CRI) were characterized with antibodies induced by immunization with synthetic peptides PSL2 and PSL3, corresponding to the second and third complementarity-determining regions (CDR) of the SIE light chain. Together with two additional RF studied previously, all seven RF belong to the V kappa IIIb sub-subgroup. The region encoded by the V kappa gene segment (positions 1 to 95) in all seven proteins was virtually identical in primary structure, whereas the sequence from positions 96 to 108 defined the usage of the J kappa 1 gene in three proteins and the J kappa 2 gene in four of them. Position 96 contributed by the recombination of the V kappa and J kappa gene segments showed the presence of four different amino acid residues. Both anti-PSL2 and anti-PSL3 bind efficiently to all separated L chains when analyzed by the Western blot technique, and the binding was inhibited specifically by the corresponding peptides. The results reveal that the majority of human IgM-RF light chains are derived from a single germ line V kappa gene or a family of closely related V kappa III germ line genes, and express two "primary structure-dependent" CRI, which are largely dependent on the amino acid sequence of the second and third light chain CDR.
Goñi
F
F
Chen
P P
PP
Pons-Estel
B
B
Carson
D A
DA
Frangione
B
B
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000032:analysis; D000918:Antibody Specificity; D003429:Cross Reactions; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007147:Immunoglobulin Light Chains / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D010446:Peptide Fragments / Q000494:pharmacology; D012217:Rheumatoid Factor / Q000032:analysis*; D005719:gamma-Globulins / Q000276:immunology
D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D010446:Peptide Fragments; D005719:gamma-Globulins; D012217:Rheumatoid Factor