The structural repertoire of the human Vκ domain

Lan M. Tomlinson, Jonathan P.L. Cox, Ermanno Gherardi, Arthur M. Lesk, Cyrus Chothia

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

In humans, the gene for the Vκ domain is produced by the recombination of one of 40 functional Vκ segments and one of five functional Jκ segments. We have analysed the sequences of these germline segments and of 736 rearranged Vκ genes to determine the repertoire of main chain conformations, or canonical structures, they encode. Over 96% of the sequences correspond to one of four canonical structures for the first antigen binding loop (L1) and one canonical structure for the second antigen binding loop (L2). Junctional diversity produces some variation in the length of the third antigen binding loop (L3) and in the identity of residues at the Vκ-Jκjoin. However, this is limited and 70% of the rearranged sequences correspond to one of three known canonical structures for the L3 region. Furthermore, we show that the canonical structures selected during the primary response are conserved during affinity maturation: the key residues that determine the conformations of the antigen binding loops are unmutated or undergo conservative mutation. The implications of these results for immune recognition are discussed.

Original languageEnglish (US)
Pages (from-to)4628-4638
Number of pages11
JournalEMBO Journal
Volume14
Issue number18
StatePublished - 1995

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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