Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions
Jönsson P., Southcombe JH., Santos AM., Huo J., Fernandes RA., McColl J., Lever M., Evans EJ., Hudson A., Chang VT., Hanke T., Godkin A., Dunne PD., Horrocks MH., Palayret M., Screaton GR., Petersen J., Rossjohn J., Fugger L., Dushek O., Xu X-N., Davis SJ., Klenerman D.
Significance The function of the T-cell coreceptor CD4 presents a long-standing puzzle. Although it is among the most potent modulators of immune responses, CD4 interacts with its binding partner, peptide-major histocompatibility class II (pMHC II), with previously unmeasurably low affinity. Here, we set a new upper limit for the solution affinity of CD4 and pMHC II and show that the two-dimensional dissociation constant in supported lipid bilayers is as much as two to three orders of magnitude higher than that for other interacting leukocyte surface proteins. These findings extend the known physical limits of functional protein interactions at the cell surface and suggest new ways that T cells may use differential receptor affinities during antigen recognition and discrimination.