T Cell Receptor Binding to a pMHCII Ligand Is Kinetically Distinct from and Independent of CD4

Abstract

Immune recognition of pMHCII ligands by a helper T lymphocyte involves its antigen-specific T cell receptor (TCR) and CD4 coreceptor. We have characterized the binding of both molecules to the same pMHCII. The D10 αβ TCR heterodimer binds to conalbumin/I-Ak with virtually identical kinetics and affinity as the single chain VαVβ domain module (scD10) (Kd = 6-8 μM). The CD4 ectodomain does not alter either interaction. Moreover, CD4 alone demonstrates weak pMHCII binding (Kd = 200 μM), with no discernable affinity for the αβ TCR heterodimer. Hence, rather than providing a major contribution to binding energy, the critical role for the coreceptor in antigen-specific activation likely results from transient inducible recruitment of the CD4 cytoplasmic tail-associated lck tyrosine kinase to the pMHCII-Iigated TCR complex.