MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition.
Antigen-specific T cell recognition is dependent on the functional density of the TCR-ligand, which consists of specific MHC molecules and a specifically bound peptide. We have examined the influence of the affinity and concentration of exogenous peptide and the density of specific MHC molecules on the proliferation of a CD4+, DQA1*0501/DQB1*0201 (DQ2.1)-restricted, HSV-2-specific T cell clone. Using antigen peptide analogs with different mutations of known DQ2-anchor residues, T cell response was reduced in an peptide-affinity and - concentration specific manner. The decrease using weaker binding peptides was gradual as stimulation with a peptide with intermediate affinity yielded intermediate T cell proliferation and the poorest binding peptide induced an even weaker T cell response. MHC class II density on the APC was modified using DQ2 homo- and heterozygous B-LCLs as APCs, however this variation of MHC concentration had no effect on T cell proliferation. We interpret this as a reflection of a low threshold for activation of the T cell clone, in which peptide-MHC avidity is the over-riding determinant of the strength of ligand signal.
Reichstetter
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Dept. of Medicine III, IZKF Erlangen, University of Erlangen-Nuremberg, Germany. sandra.reichstetter@med3.med.uni-erlangen.de
Kwok
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Kochik
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Koelle
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Beaty
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Nepom
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D000483:Alleles; D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D002455:Cell Division; D002461:Cell Line, Transformed; D006683:HLA-DQ Antigens / Q000276:immunology*; D059866:HLA-DQ beta-Chains; D017405:Herpes Simplex Virus Protein Vmw65 / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D017405:Herpes Simplex Virus Protein Vmw65; D008024:Ligands; D010455:Peptides