Human anti-Gal heavy chain genes

Preferential use of V(H)3 and the presence of somatic mutations

L. Wang, Marko Radic, U. Galili

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Anti-Gal is the most abundant natural Ab known in humans. It interacts specifically with the carbohydrate structure Galα1-3Galβ1-4GlcNAc-R (termed the α-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(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(H) genes were sequenced. The affinity of anti-Gal clones for the free radiolabeled α- galactosyl epitope ranged between 1.1 x 106 M-1 and 5 x 108 M-1. Eight of the nine clones studied used V(H)3 family genes and one clone used a V(H)1 family gene. Four of the five V(H)3 genes used were found to form a cluster of related sequences, suggesting that functional constraints may lead to the use of V(H)3 genes with structural motifs that are suited for specific interactions with the α-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(H) genes undergo somatic mutations. These somatic mutations may provide a pool of variants that are available for affinity maturation.

Original languageEnglish (US)
Pages (from-to)1276-1285
Number of pages10
JournalJournal of Immunology
Volume155
Issue number3
StatePublished - Jan 1 1995

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Mutation
Clone Cells
Genes
Epitopes
Cercopithecidae
Hominidae
Human Herpesvirus 4
Germ Cells
B-Lymphocytes
Carbohydrates
Serum

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Human anti-Gal heavy chain genes : Preferential use of V(H)3 and the presence of somatic mutations. / Wang, L.; Radic, Marko; Galili, U.

In: Journal of Immunology, Vol. 155, No. 3, 01.01.1995, p. 1276-1285.

Research output: Contribution to journalArticle

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