Sequence variation among heavy chains from inulin-binding myeloma proteins.
The entire sequences of the variable region of four heavy chains from BALB/c inulin-binding myeloma proteins have been determined. Among the four proteins there are six amino acid differences, all of which occur in the framework portion of the variable region. All of the six amino acid substitutions can be explained by single base mutations at the DNA level. The pattern of diversity in these proteins is compared to a previously reported group of heavy chains from phosphorylcholine-binding myeloma proteins. Unlike the phosphorylcholine-binding proteins, which (with the exception of two that are identical) have size and sequence differences in their complementarity regions, the inulin-binding heavy chains all have identical complementarity regions with H3 being extremely short. The pattern of variation observed in the anti-inulin heavy chains appears to be most easily explained by a somatic mutation mechanism. However, because none of the substitutions occur in complementarity-determining regions, they presumably would have no selective advantage and would not alter binding specificity. These proteins have further been shown to have crossreacting antigenic determinants (idiotypes). Five of the six sequence differences observed occur at positions that are internal in the molecule and thus presumably would not account for the idiotypic differences. These results suggest that most of the observed idiotypic crossreactivities will be due to differences in the light chains of the anti-inulin proteins.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001666:Binding Sites, Antibody; D005796:Genes; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region; D007444:Inulin / Q000276:immunology*; D051379:Mice; D009194:Myeloma Proteins / Q000235:genetics*; D010446:Peptide Fragments; D010767:Phosphorylcholine / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009194:Myeloma Proteins; D010446:Peptide Fragments; D010767:Phosphorylcholine; D007444:Inulin