The crystal structure of a complex involving the D10 T cell receptor (TCR),
16-residue foreign peptide antigen, and the I-A(k) self major histocompati
bility complex (MHC) class II molecule is reported at 3.2 angstrom resoluti
on. The D10 TCR is oriented in an orthogonal mode relative to its peptide-M
HC (pMHC) Ligand, necessitated by the amino-terminal extension of peptide r
esidues projecting from the MHC class II antigen-binding groove as part of
a mini beta sheet. Consequently, the disposition of D10 complementarity-det
ermining region Loops is altered relative to that of most pMHCI-specific TC
Rs; the Latter TCRs assume a diagonal orientation, although with substantia
l variability. Peptide recognition, which involves P-1 to P8 residues, is d
ominated by the V alpha domain, which also binds to the class II MHC beta(1
) helix. That docking is Limited to one segment of MHC-bound peptide offers
an explanation for epitope recognition and altered peptide Ligand effects,
suggests a structural basis for alloreactivity, and illustrates how bacter
ial superantigens can span the TCR-pMHCII surface.