A cDNA sequence encoding a rabbit heavy chain variable region of the V_Ha2 allotype showing homologies with human heavy chain sequences

Abstract

There are only four positions in the amino acid sequences of immunoglobulin variable region domains of all species at which the same amino acid is always found¹. The compiled sequences of rabbit heavy chain variable (V_H) domains have 48 invariant positions^1,2 and at 14 additional positions in the first and third framework segments the different amino acids found correlate with the rabbits' V_Ha allotype^3–5. This V_H allotypic system with three common ‘alleles’ V_Ha1, V_Ha2 and V_Ha3 inherited in simple mendelian fashion^3,4 poses the question of how gene families with distinct sets of conserved codons have evolved and been maintained in the midst of information leading to hypervariability. Here we report a cDNA sequence that encodes a protein characteristic of the rabbit V_Ha2 allotype and we predict the allotype-associated codons that may be found in V_Ha1 and V_Ha3 genes. We have also found within the second hypervariable, complementarity-determining region (CDR2) encoded by our cDNA clone, a DNA sequence highly homologous to a human D_H minigene⁶. This observation and a similar one of Wu and Kabat⁷, who identified a D_H minigene sequence in the CDR2 of a cloned human V_H gene⁸, lends support to their idea that D minigene information has contributed to CDR2 either during evolution or ontogeny⁷. Gene conversion^9,10, minigene assortment^11,12 or insertion¹³ mechanisms may be involved both in the generation of hypervariability and the conservation of allotype codons.