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Human anti-Gal heavy chain genes. Preferential use of V sub(H)3 and the presence of somatic mutations
Journal article   Open access   Peer reviewed

Human anti-Gal heavy chain genes. Preferential use of V sub(H)3 and the presence of somatic mutations

Le Wang, M Radic and U Galili
The Journal of immunology (1950), v 155(3), pp 1276-1285
01 Aug 1995
url
https://doi.org/10.4049/jimmunol.155.3.1276View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

alpha -galactosyl epitope heavy chains immunoglobulins lymphocytes B man Genes Mutation
Anti-Gal is the most abundant natural Ab known in humans. It interacts specifically with the carbohydrate structure Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha -galactosyl epitope), constitutes approximately 1% of circulating Ig, and is found in all three isotypes in the serum. Anti-Gal is produced in Old World monkeys, apes, and humans, and in no other mammalian species. The objective of this study was to determine the V sub(H) genes involved in the synthesis of anti-Gal. B lymphocytes from various individuals were transformed by EBV, the clones producing anti-Gal were isolated, the specificity and affinity of the Abs were determined, and the V sub(H) genes were sequenced. The affinity of anti-Gal clones for the free radiolabeled alpha -galactosyl epitope ranged between 1.1 x 10 super(6) M super(-1) and 5 x 10 super(8) M super(-1). Eight of the nine clones studied used V sub(H)3 family genes and one clone used a V sub(H)1 family gene. Four of the five V sub(H)3 genes used were found to form a cluster of related sequences, suggesting that functional constraints may lead to the use of V sub(H)3 genes with structural motifs that are suited for specific interactions with the alpha -galactosyl epitope. Comparison with known germline sequences for all of the clones studied and analysis of autologous germ-line genes in two of the clones indicate that anti-Gal V sub(H) genes undergo somatic mutations. These somatic mutations may provide a pool of variants that are available for affinity maturation.

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