Epitopes described in "Altered ligands reveal limited plasticity in the T cell response to a pathogenic epitope."

Article Authors:S Pingel; P Launois; D J Fowell; C W Turck; S Southwood; A Sette; N Glaichenhaus; J A Louis; R M Locksley
Article Title:Altered ligands reveal limited plasticity in the T cell response to a pathogenic epitope.
Reference Detail
Reference ID:200104
Abstract:Experimental leishmaniasis offers a well characterized model of T helper type 1 cell (Th1)-mediated control of infection by an intracellular organism. Susceptible BALB/c mice aberrantly develop Th2 cells in response to infection and are unable to control parasite dissemination. The early CD4(+) T cell response in these mice is oligoclonal and reflects the expansion of Vbeta4/ Valpha8-bearing T cells in response to a single epitope from the parasite Leishmania homologue of mammalian RACK1 (LACK) antigen. Interleukin 4 (IL-4) generated by these cells is believed to direct the subsequent Th2 response. We used T cells from T cell receptor-transgenic mice expressing such a Vbeta4/Valpha8 receptor to characterize altered peptide ligands with similar affinity for I-Ad. Such altered ligands failed to activate IL-4 production from transgenic LACK-specific T cells or following injection into BALB/c mice. Pretreatment of susceptible mice with altered peptide ligands substantially altered the course of subsequent infection. The ability to confer a healer phenotype on otherwise susceptible mice using altered peptides that differed by a single amino acid suggests limited diversity in the endogenous T cell repertoire recognizing this antigen.
Affiliations:Departments of Medicine, Microbiology, and Immunology, University of California San Francisco, San Francisco, California 94143, USA.
Reference Type:Literature
PubMed ID:10190902
Journal:J Exp Med
Journal Volume:189
Article Pages:1111-20
Journal ISSN:0022-1007
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@7b736006;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@53a5693b;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@109fcb64;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@6ae21ac2;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@224aed60;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@65264b36;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@3513fa1b;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@32891dd6;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4805e685;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@7b614ab3;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@306f6d0d;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@63608952
Article MeSH List:Amino Acid Sequence; Amino Acid Substitution; Animals; Antigens, Protozoan(immunology); Disease Susceptibility; Epitopes(immunology); Female; Histocompatibility Antigens Class II(immunology); Immune Tolerance; Immunity, Cellular; Interferon-gamma(secretion); Interleukin-4(secretion); Leishmania major(immunology); Leishmaniasis, Cutaneous(immunology); Ligands; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Peptide Fragments(chemical synthesis; immunology); Protozoan Proteins(chemistry; immunology); Receptors, Antigen, T-Cell, alpha-beta(genetics; immunology); Recombinant Fusion Proteins(immunology); Superantigens(immunology); Th2 Cells(immunology)
Curation Last Updated:2015-01-17 21:00:27