An αβ T Cell Receptor Structure at 2.5 Å and Its Orientation in the TCR-MHC Complex

The central event in the cellular immune response to invading microorganisms is the specific recognition of foreign peptides bound to major histocompatibility complex (MHC) molecules by the alpha beta T cell receptor (TCR). The x-ray structure of the complete extracellular fragment of a glycosylated alpha beta TCR was determined at 2.5 angstroms, and its orientation bound to a class I MHC-peptide (pMHC) complex was elucidated from crystals of the TCR-pMHC complex. The TCR resembles an antibody in the variable V alpha and V beta domains but deviates in the constant C alpha domain and in the interdomain pairing of C alpha with C beta. Four of seven possible asparagine-linked glycosylation sites have ordered carbohydrate moieties, one of which lites in the C alpha-C beta interface. The TCR combining site is relatively flat except for a deep hydrophobic cavity between the hypervariable CRD3s (complementarity-determining regions) of the alpha and beta chains. The 2C TCR covers the class I MHC H-2K(b) binding groove so that the V alpha CDRs 1 and 2 are positioned over the amino-terminal region of the bound dEV8 peptide, the V beta chain CDRs 1 and 2 are over the carboxy-terminal region of the peptide, and the V alpha and V beta CDR3s straddle the peptide between the helices around the central position of the peptide.