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MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition.
Title | MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition. |
Publication Type | Journal Article |
Year of Publication | 1999 |
Authors | Reichstetter, S, Kwok, WW, Kochik, S, Koelle, DM, Beaty, JS, Nepom, GT |
Journal | Hum Immunol |
Volume | 60 |
Issue | 7 |
Pagination | 608-18 |
Date Published | 1999 Jul |
ISSN | 0198-8859 |
Keywords | Alleles, Amino Acid Sequence, Antigen-Presenting Cells, Antigens, Viral, Cell Division, Cell Line, Transformed, Herpes Simplex Virus Protein Vmw65, Herpesvirus 2, Human, HLA-DQ Antigens, HLA-DQ beta-Chains, Humans, Ligands, Lymphocyte Activation, Molecular Sequence Data, Peptides, T-Lymphocytes |
Abstract | 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. |
Alternate Journal | Hum. Immunol. |
PubMed ID | 10426278 |