A cDNA sequence encoding a rabbit heavy chain variable region of the VHa2 allotype showing homologies with human heavy chain sequences

作者:

KE BernsteinEP ReddyCB AlexanderRG Mage

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摘要:

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 found 1 . 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 H a allotype 3–5 . This V H allotypic system with three common 'alleles' V H a1 , V H a2 and V H a3 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 H a2 allotype and we predict the allotype-associated codons that may be found in V H a1 and V H a3 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 minigene 6 . This observation and a similar one of Wu and Kabat 7 , who identified a D H minigene sequence in the CDR2 of a cloned human V H gene 8 , lends support to their idea that D minigene information has contributed to CDR2 either during evolution or ontogeny 7 . Gene conversion 9,10 , minigene assortment 11,12 or insertion 13 mechanisms may be involved both in the generation of hypervariability and the conservation of allotype codons.

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DOI:

10.1038/300074a0

被引量:

1104

年份:

1982

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1985
被引量:124

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