Complete amino acid sequence of light chain variable regions derived from five monoclonal anti-p-azophenylarsonate antibodies differing with respect to a crossreactive idiotype

The induced antibody response to the hapten p-azophenylarsonate in the A/J mouse has provided a model system for the detailed examination of a heritable crossreactive idiotype and its fine structural and serologic analysis. While earlier studies used the apparent homogeneity in the serum response for structural studies, a more complete understanding of the arsonate idiotypic system became possible with the development of monoclonal antibodies differing with respect to these determinants. Five monoclonal antibodies, four crossreactive idiotype positive and one crossreactive idiotype negative, were selected for complete amino acid sequence analysis. The sequences of the light chain variable regions of these molecules are presented here. The data indicate considerable sequence divergence of the monoclonal light chains from the serum light chains. However, there is a striking degree of homology among the monoclonal light chains regardless of the idiotype character of the parent molecule. Although minor variations are apparent throughout the variable regions, the joining regions are identical among light chains in all of these anti-arsonate antibodies. A particularly notable focus of variation is found at positions 92 and 93 in the third hypervariable region. The possible role of this region in the contribution of the light chain to the arsonate crossreactive idiotype is discussed. These data are consistent with the concept that the anti-arsonate monoclonal light chains originate from the joining of a specific J[K] gene segment to a single germ-line V[K] gene segment. These coding segments are likely further subject to a variety of somatic alterations that generate the modest sequence diversity found among the final protein products.