Altered ligands reveal limited plasticity in the T cell response to a pathogenic epitope

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 ce...

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Veröffentlicht in:The Journal of experimental medicine Jg. 189; H. 7; S. 1111
Hauptverfasser: Pingel, S, Launois, P, Fowell, D J, Turck, C W, Southwood, S, Sette, A, Glaichenhaus, N, Louis, J A, Locksley, R M
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 05.04.1999
Schlagworte:
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 - metabolism
Interleukin-4 - metabolism
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
ISSN:0022-1007
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-2
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0022-1007
DOI:10.1084/jem.189.7.1111