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 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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigen Presentation*
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CD4 Antigens / genetics
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CD4 Antigens / metabolism*
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Genes, MHC Class II
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Histocompatibility Antigens Class II*
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Humans
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Kinetics
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Ligands
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Lymphocyte Activation
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Models, Immunological
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Peptides / metabolism*
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Protein Binding
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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T-Lymphocytes, Helper-Inducer / immunology*
Substances
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CD4 Antigens
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Histocompatibility Antigens Class II
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I-Ak antigen
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Ligands
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Peptide Fragments
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Peptides
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta
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Recombinant Fusion Proteins