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 Vβ4/ Vα8-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 Vβ4/Vα8 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.
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5 April 1999
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April 05 1999
Altered Ligands Reveal Limited Plasticity in the T Cell Response to a Pathogenic Epitope
Sabine Pingel,
Sabine Pingel
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Pascal Launois,
Pascal Launois
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Deborah J. Fowell,
Deborah J. Fowell
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Christoph W. Turck,
Christoph W. Turck
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Scott Southwood,
Scott Southwood
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Alessandro Sette,
Alessandro Sette
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Nicolas Glaichenhaus,
Nicolas Glaichenhaus
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Jacques A. Louis,
Jacques A. Louis
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Richard M. Locksley
Richard M. Locksley
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
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Sabine Pingel
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Pascal Launois
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Deborah J. Fowell
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Christoph W. Turck
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Scott Southwood
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Alessandro Sette
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Nicolas Glaichenhaus
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Jacques A. Louis
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Richard M. Locksley
From the *Departments of Medicine, Microbiology, and Immunology and the ‡Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; §World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges CH-1066, Switzerland; ‖Cytel Corporation, San Diego, California 92121; and the ¶Institute of Molecular and Cellular Pharmacology, University of Nice, Valbonne 06560, France
Address correspondence to Richard M. Locksley, UCSF, Box 0654, C-443, 521 Parnassus Ave., San Francisco, CA 94143. Phone: 415-476-5859; Fax: 415-476-9364; E-mail: [email protected] or Jacques A. Louis, WHO Research and Training Center, University of Lausanne, Epalinges, Switzerland. Phone: 41-21-692-5703; Fax: 41-21-692-5705; E-mail: [email protected]
S. Pingel and P. Launois contributed equally to this work.
Received:
October 23 1998
Revision Received:
February 12 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (7): 1111–1120.
Article history
Received:
October 23 1998
Revision Received:
February 12 1999
Citation
Sabine Pingel, Pascal Launois, Deborah J. Fowell, Christoph W. Turck, Scott Southwood, Alessandro Sette, Nicolas Glaichenhaus, Jacques A. Louis, Richard M. Locksley; Altered Ligands Reveal Limited Plasticity in the T Cell Response to a Pathogenic Epitope . J Exp Med 5 April 1999; 189 (7): 1111–1120. doi: https://doi.org/10.1084/jem.189.7.1111
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