Figure 1.

The CD4 co-receptor binds to class II but not class I MHC molecules. (A) Superposition of selected MHCII molecules onto the structure of the MHCII molecule DR1 in complex with the N-terminal two-domain of CD4 (PDB code: 3S5L). The superposition is based on the α2 domain. In all cases, the MHCII molecules can accommodate the CD4 N-terminal domain for binding. (B) Two MHCI molecules are superimposed onto the DR1-CD4 complex structure. Here the β2M domain of MHCI was overlaid on the α2 domain of DR1 molecule. These two selected MHCI molecules have the largest (1AGF, in blue) and smallest (1QVO, in yellow) opening angle, respectively, between the two membrane-proximal domains, α3 and β2M. Compared with the MHCII DR1-CD4 complex, they do not have a sufficiently large opening angle to accommodate CD4. (C) Close-up of (B).