Research Article

Structural Basis of Plasticity in T Cell Receptor Recognition of a Self Peptide-MHC Antigen

Science  20 Feb 1998:
Vol. 279, Issue 5354, pp. 1166-1172
DOI: 10.1126/science.279.5354.1166

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


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 Vα 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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: wilson{at}

View Full Text

Cited By...