Crystal structure of a human CD3- dimer in complex with a UCHT1 single-chain antibody fragment

The T cell receptor complex transmits signals from MHC peptide antigens through a set of constitutively associated signaling molecules, including CD3and CD3. We report the crystal structure at 1.9-Å resolution of a complex between a human CD3ectodomain heterodimer and a single-chain fragment of the UCHT1 antibody. CD3and CD3share a conserved interface between the Ig-fold ectodomains, with parallel packing of the two G strands. CD3has a more electronegative surface and a more compact Ig fold than CD3; thus, the two CD3 heterodimers have distinctly different molecular surfaces. The UCHT1 antibody binds near an acidic region of CD3opposite 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 CD3structure completes the set of TCR CD3 globular ectodomains and contributes information about exposed CD3 surfaces.