The structural repertoire of the human V(κ) domain

I. M. Tomlinson, J. P.L. Cox, E. Gherardi, A. M. Lesk, C. Chothia

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In humans, the gene for the V(κ) domain is produced by the recombination of one of 40 functional V(κ) segments and one of five functional J(κ) segments. We have analysed the sequences of these germline segments and of 736 rearranged V(κ) 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 V(κ)-J(κ) join. 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
Issue number18
StatePublished - 1995

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Tomlinson, I. M., Cox, J. P. L., Gherardi, E., Lesk, A. M., & Chothia, C. (1995). The structural repertoire of the human V(κ) domain. EMBO Journal, 14(18), 4628-4638.