Altered Ligands Reveal Limited Plasticity in the T Cell Response to a Pathogenic Epitope
1999; Rockefeller University Press; Volume: 189; Issue: 7 Linguagem: Inglês
10.1084/jem.189.7.1111
ISSN1540-9538
AutoresSabine Pingel, Pascal Launois, Deborah J. Fowell, Christoph W. Turck, Scott Southwood, Alessandro Sette, Nicolas Glaichenhaus, Jacques Louis, Richard M. Locksley,
Tópico(s)T-cell and B-cell Immunology
ResumoExperimental 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.
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