Article: article from journal or magazin.
Altered ligands reveal limited plasticity in the T cell response to a pathogenic epitope.
Journal of Experimental Medicine
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.
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, Peptide Fragments/immunology, Protozoan Proteins/chemistry, Protozoan Proteins/immunology, Receptors, Antigen, T-Cell, alpha-beta/genetics, Receptors, Antigen, T-Cell, alpha-beta/immunology, Recombinant Fusion Proteins/immunology, Superantigens/immunology, Th2 Cells/immunology
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