Article

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

Department of Molecular Biology and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science (impact factor: 31.2). 03/1998; 279(5354):1166-72. pp.1166-72
Source: PubMed

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.

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Keywords

alloreactive 2C TCR
 
anisotropic 3.0 angstrom resolution x-ray data
 
CDR3
 
dEV8 peptide
 
different peptide antigens
 
different peptides
 
Extensive TCR interaction
 
foreign pathogens
 
generalized orientation
 
Large conformational changes
 
low-affinity MHC structural framework
 
molecular basis
 
peptide
 
self peptide-major histocompatibility complex
 
self-antigens
 
signaling
 
slight additional kinetic stabilization
 
structural plasticity
 
TCR beta chain complementarity-determining region 3
 
Valpha domain