The structural basis of a hapten-inhibitable kappa-chain idiotype
Vrana, M.; Rudikoff, S.; Potter, M.
Journal of Immunology 122(5): 1905-1910
1979
ISSN/ISBN: 0022-1767 PMID: 109517 Document Number: 153689
The complete .kappa.-chain variable region sequences from 2 murine myeloma proteins (U-61 and E-109) with binding specificity for .beta.(2-1) fructofuranosyl moieties were determined. The 2 .kappa.-chains differed from each other by 4 amino acids. Earlier studies with recombinant molecules assigned 3 different idiotypes to these 2 L chains. One of these determinants was hapten inhibitable and was presumed to be in or near the combining site, whereas the remaining 2 were not hapten inhibitable. Analysis of the 4 sequence differences found between these 2 chains in conjunction with a hypothetical 3-dimensional model of the anti-fructan antibodies revealed that the hapten-inhibitable idiotype appeared to be determined by the association of 2 amino acids found in complementarity-determining regions I and III. One of the nonhapten-inhibitable determinants was caused by the 3 substitutions occurring in the framework portion of the variable region. The 2nd of these determinants appeared to result from the 3-dimensional proximity of more than 1 framework amino acid. A comparison of the U-61 and E-109 structures with partial sequences from several other L chains from fructofuranose-binding proteins revealed 8 differences occurring in framework and complementarity-determining regions. The identification of serine in 2 proteins at residue 30 and asparagine at this position in 3 other proteins suggested that despite the great degree of homology exhibited by these L chains at least 2 germline genes are required to code for these molecules.