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SignificanceThe 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.

Original publication




Journal article


Proceedings of the National Academy of Sciences


Proceedings of the National Academy of Sciences

Publication Date





5682 - 5687