Structure of the Vδ domain of a human γδ T-cell antigen receptor

Hongmin Li, Marina I. Lebedeva, Andrea S. Llera, Barry A. Fields, Michael B. Brenner, Roy A. Mariuzza

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Antigen recognition by T lymphocytes is mediated by cell-surface glycoproteins known as T-cell antigen receptors (TCRs). These are composed of α and β, or γ and δ, polypeptide chains with variable (V) and constant (C) regions. In contrast to αβ TCRs, which recognize antigen only as peptide fragments bound to molecules of the major histocompatibility complex (MHC), γδ TCRs appear to recognize proteins directly, without antigen processing, and to recognize MHC molecules independently of the bound peptide. Moreover, small phosphate-containing non-peptide compounds have also been identified as ligands for certain γδ T cells. These studies indicate that antigen recognition by γδ TCRs may be fundamentally different from that by αβ TCRs. The three-dimensional structures of several αβ TCRs and TCR fragments, and their complexes with peptide-MHC or superantigens, have been determined. Here we report the crystal structure of the Vδ domain of a human γδ TCR at 1.9 Å resolution. A comparison with antibody and αβ TCR V domains reveals that the framework structure of Vδ more closely resembles that of VH than of Vα, Vβ or VL (where H and L refer to heavy and light chains), whereas the relative positions and conformations of its complementarity-determining regions (CDRs) share features of both Vα and VH. These results provide the first direct evidence that γδ TCRs are structurally distinct from αβ TCRs and, together with the observation that the CDR3 length distribution of TCR δ chains is similar to that of immunoglobulin heavy chains, are consistent with functional studies suggesting that recognition of certain antigens by γδ TCRs may resemble antigen recognition by antibodies.

Original languageEnglish (US)
Pages (from-to)502-506
Number of pages5
JournalNature
Volume391
Issue number6666
DOIs
StatePublished - Jan 29 1998
Externally publishedYes

ASJC Scopus subject areas

  • General

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