Inhibition of naïve class I-restricted T cells by altered peptide ligands.
Amino acid variants of an antigenic peptide or altered peptide ligands have previously been investigated with CD4+ and CD8+ T cells. However, for CD8+ T cells, only clones (which are continually restimulated in vitro) have been assessed. Using TCR transgenic mice specific for a class I Kb-restricted OVA peptide (OVAp; OT-I mice) as a source of naïve CD8+ T cells, single amino acid variants of the OVAp were analysed in vitro for their ability to antagonize the proliferative and cytotoxic function of naïve OT-I cells. Peptides with substitutions at TCR contact residues were found to be the most potent antagonists of OT-I cell function. Those peptides that inhibited activation of cells to proliferate also inhibited activation of cells to become killers. Inhibition was inversely correlated with interferon (IFN)-gamma production. It was found that levels of antagonist peptide required for inhibition were higher than that described for T cell clones, presumably due to affinity differences.
Koniaras
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C
The Walter and Eliza Hall Institute, Monash Medical School, Melbourne, Victoria, Australia.
Carbone
F R
FR
Heath
W R
WR
Lew
A M
AM
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin