T Cell Receptor Binding to a pMHCII Ligand Is Kinetically Distinct from and Independent of CD4.
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 alphabeta TCR heterodimer binds to conalbumin/I-A(k) with virtually identical kinetics and affinity as the single chain ValphaVbeta domain module (scD10) (Kd = 6-8 microm). The CD4 ectodomain does not alter either interaction. Moreover, CD4 alone demonstrates weak pMHCII binding (Kd = 200 microm), with no discernable affinity for the alphabeta 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-ligated TCR complex.
Xiong
Y
Y
Laboratory of Immunobiology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kern
P
P
Chang
H
H
Reinherz
E
E
D017951:Antigen Presentation; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008213:Lymphocyte Activation; D018448:Models, Immunological; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D008024:Ligands; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins