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

K. Christopher Garcia, Massimo Degano, Larry R. Pease, Mingdong Huang, Per A. Peterson, Luc Teyton, Ian A. Wilson

Research output: Contribution to journalArticle

562 Citations (Scopus)

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 β 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 α helices suggests a generalized orientation that is mediated by the V(α) 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.

Original languageEnglish
Pages (from-to)1166-1172
Number of pages7
JournalScience
Volume279
Issue number5354
DOIs
Publication statusPublished - Feb 20 1998

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T-Cell Antigen Receptor
Antigens
Peptides
Major Histocompatibility Complex
Complementarity Determining Regions
Peptide T
Histocompatibility Antigens
Autoantigens
Cell Communication
Thymus Gland
X-Rays
T-Lymphocytes

ASJC Scopus subject areas

  • General

Cite this

Garcia, K. C., Degano, M., Pease, L. R., Huang, M., Peterson, P. A., Teyton, L., & Wilson, I. A. (1998). Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science, 279(5354), 1166-1172. https://doi.org/10.1126/science.279.5354.1166

Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. / Garcia, K. Christopher; Degano, Massimo; Pease, Larry R.; Huang, Mingdong; Peterson, Per A.; Teyton, Luc; Wilson, Ian A.

In: Science, Vol. 279, No. 5354, 20.02.1998, p. 1166-1172.

Research output: Contribution to journalArticle

Garcia, KC, Degano, M, Pease, LR, Huang, M, Peterson, PA, Teyton, L & Wilson, IA 1998, 'Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen', Science, vol. 279, no. 5354, pp. 1166-1172. https://doi.org/10.1126/science.279.5354.1166
Garcia, K. Christopher ; Degano, Massimo ; Pease, Larry R. ; Huang, Mingdong ; Peterson, Per A. ; Teyton, Luc ; Wilson, Ian A. / Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. In: Science. 1998 ; Vol. 279, No. 5354. pp. 1166-1172.
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