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Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen

Academic Article
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Overview

authors

  • Garcia, K. C.
  • Degano, M.
  • Pease, L. R.
  • Huang, M. D.
  • Peterson, P. A.
  • Teyton, Luc
  • Wilson, Ian

publication date

  • 1998

journal

  • Science  Journal

abstract

  • The T cell receptor (TCR) inherently has dual specificity. T cells must recognize self-antigens in the thymus during maturation and then discriminate between foreign pathogens in the periphery. A molecular basis for this cross-reactivity is elucidated by the crystal structure of the alloreactive 2C TCR bound to self peptide-major histocompatibility complex (pMHC) antigen H-2Kb-dEV8 refined against anisotropic 3.0 angstrom resolution x-ray data. The interface between peptide and TCR exhibits extremely poor shape complementarity, and the TCR beta chain complementarity-determining region 3 (CDR3) has minimal interaction with the dEV8 peptide. Large conformational changes in three of the TCR CDR loops are induced upon binding, providing a mechanism of structural plasticity to accommodate a variety of different peptide antigens. Extensive TCR interaction with the pMHC alpha helices suggests a generalized orientation that is mediated by the Valpha domain of the TCR and rationalizes how TCRs can effectively "scan" different peptides bound within a large, low-affinity MHC structural framework for those that provide the slight additional kinetic stabilization required for signaling.

subject areas

  • Animals
  • Crystallization
  • Crystallography, X-Ray
  • H-2 Antigens
  • Ligands
  • Mice
  • Mice, Transgenic
  • Models, Molecular
  • Mutation
  • Oligopeptides
  • Protein Conformation
  • Protein Structure, Secondary
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombinant Proteins
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Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.279.5354.1166

PubMed ID

  • 9469799
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Additional Document Info

start page

  • 1166

end page

  • 1172

volume

  • 279

issue

  • 5354

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