Canonical structures for the hypervariable regions of T cell αβ receptors

Bissan Al-Lazikani, Arthur M. Lesk, Cyrus Chothia

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


T cell αβ receptors have binding sites for peptide-MHC complexes formed by six hypervariable regions. Analysis of the six atomic structures known for Vα and for Vβ domains shows that their first and second hypervariable regions have one of three or four different main-chain conformations (canonical structures). Six of these canonical structures have the same conformation in complexes with peptide-MHC complexes, the free receptor and/or in an isolated V domain. Thus, for at least the first and second hypervariable regions in the currently known structures, the conformation of the canonical structures is well defined in the free state and is conserved on formation of complexes with peptide-MHC. We identified the key residues that are mainly responsible for the conformation of each canonical structure. The first and second hypervariable regions of Vα and Vβ domains are encoded by the germline V segments. Humans have 37 functional Vα segments and 47 Vβ segments, and mice have 20 Vβ segments. Inspection of the size of their hypervariable regions, and of sites that contain key residues, indicates that close to 70 % of Vα segments and 90 % of Vβ segments have hypervariable regions with a conformation of one of the known canonical structures. The α and β V gene segments in both humans and mice have only a few combinations of different canonical structure in their first and second hyper-variable regions. In human Vβ domains, the number of different sequences with these canonical structure combinations is larger than in mice, whilst for Vα domains it is probably smaller. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)979-995
Number of pages17
JournalJournal of Molecular Biology
Issue number4
StatePublished - Jan 28 2000

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology


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