Crystal structure of a human CD3-epsilon/delta dimer in complex with a UCHT1 single-chain antibody fragment.
The alpha/beta T cell receptor complex transmits signals from MHC/peptide antigens through a set of constitutively associated signaling molecules, including CD3-epsilon/gamma and CD3-epsilon/delta. We report the crystal structure at 1.9-A resolution of a complex between a human CD3-epsilon/delta ectodomain heterodimer and a single-chain fragment of the UCHT1 antibody. CD3-epsilon/delta and CD3-epsilon/gamma share a conserved interface between the Ig-fold ectodomains, with parallel packing of the two G strands. CD3-delta has a more electronegative surface and a more compact Ig fold than CD3-gamma; thus, the two CD3 heterodimers have distinctly different molecular surfaces. The UCHT1 antibody binds near an acidic region of CD3-epsilon opposite the dimer interface, occluding this region from direct interaction with the TCR. This immunodominant epitope may be a uniquely accessible surface in the TCR/CD3 complex, because there is overlap between the binding site of the UCHT1 and OKT3 antibodies. Determination of the CD3-epsilon/delta structure completes the set of TCR/CD3 globular ectodomains and contributes information about exposed CD3 surfaces.
Arnett
Kelly L
KL
Department of Biological Chemistry and Molecular Pharmacology, Howard Hughes Medical Institute, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA. arnett@crystal.harvard.edu
Harrison
Stephen C
SC
Wiley
Don C
DC
D017252:CD3 Complex / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D008958:Models, Molecular; D046912:Multiprotein Complexes; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D055672:Static Electricity
D017252:CD3 Complex; C115335:CD3E protein, human; C472562:CD3delta antigen; D007128:Immunoglobulin Fragments; D046912:Multiprotein Complexes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C055966:immunoglobulin Fv