Structural and serological analysis of cross-reactive idiotypes: comparison of heavy and light chain families of anti-arsonate antibodies.

The amino acid sequences of VH and VL regions of 16 cross-reactive idiotype-positive (CRI+) and ten CRI-negative (CRI-) monoclonal anti-arsonate antibodies from a range of laboratories were compared. Analysis of the data demonstrates the existence of several pairs of hybridoma proteins (within CRI+ and CRI- families) which have identical or very similar sequences for VH and VL. This strongly suggests the existence of at least 4 germ-line genes in A/J mice coding for CRI+VH, CRI+VL, CRI-VH and CRI-VL regions. The CRI+ family, however, consists of VH structures which represent either (1) germ-line sequences, (2) VHVL variants with a few substitutions, or (3) VHVL variants with extensive substitutions. The latter two consist of antibodies which have lost either the CRI or arsonate binding capacities. The CRI- family consists of two very different groups. The first group appears to be the product of CRI- VHVL germ-line genes and their variants. The second group contains antibodies coded by CRI+ germ-line genes but which, due to somatic diversification, become CRI-. Comparison of VHVL of all anti-arsonate antibodies clearly indicates that light chain selection by the heavy chain is a non-random process. Also, there appears to be a parallel diversification of VH and VL. Comparative data on H and L chain structures and serological evidence obtained by three monoclonal antiidiotypic antibodies indicates that formation of the original cross-reactive idiotypic determinant(s) requires an equal contribution for both H and L chains; moreover, CRI consists of a single (or few) idiotopes.