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 (VH) domains have 48 invariant positions1,2 and at 14 additional positions in the first and third framework segments the different amino acids found correlate with the rabbits' VHa allotype3–5. This VH allotypic system with three common ‘alleles’ VHa1, VHa2 and VHa3 inherited in simple mendelian fashion3,4 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 VHa2 allotype and we predict the allotype-associated codons that may be found in VHa1 and VHa3 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 DH minigene6. This observation and a similar one of Wu and Kabat7, who identified a DH minigene sequence in the CDR2 of a cloned human VH gene8, lends support to their idea that D minigene information has contributed to CDR2 either during evolution or ontogeny7. Gene conversion9,10, minigene assortment11,12 or insertion13 mechanisms may be involved both in the generation of hypervariability and the conservation of allotype codons.
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Bernstein, K., Reddy, E., Alexander, C. et al. A cDNA sequence encoding a rabbit heavy chain variable region of the VHa2 allotype showing homologies with human heavy chain sequences. Nature 300, 74–76 (1982). https://doi.org/10.1038/300074a0
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DOI: https://doi.org/10.1038/300074a0
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