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Modulation of T cell development by an endogenous altered peptide ligand
B L Hsu1, B D Evavold, P M Allen
1Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110.
The Journal of Experimental Medicine
|February 1, 1995
Summary
Endogenous peptides profoundly impact T cell development. An altered peptide ligand (Ser69) acted as an agonist, while the original ligand (Hbd 64-76) became an antagonist, shaping the T cell repertoire.
Area of Science:
- Immunology
- T cell biology
- Peptide-MHC interactions
Background:
- T cells encounter numerous endogenous peptides during thymic and peripheral selection.
- Understanding how these peptides influence T cell development is crucial for immunology.
Purpose of the Study:
- To investigate the impact of an endogenous peptide on T cell development in vivo.
- To explore how altered peptide ligands affect T cell repertoire selection.
Main Methods:
- Utilized a T cell receptor (TCR) transgenic mouse model.
- Studied T cell reactivity to Ser69 and Hbd (64-76) peptides.
- Analyzed T cell populations based on avidity and ligand specificity.
Main Results:
- A transgenic mouse model unexpectedly developed reactivity to Ser69 peptide, an altered peptide ligand.
- Two Ser69-reactive T cell populations emerged: one cross-reactive, the other Ser69-specific.
- Hbd (64-76) acted as a specific TCR antagonist for Ser69-only-reactive T cells.
- Endogenous antagonist presentation in the thymus eliminated high-avidity T cells, sparing low-avidity ones.
Conclusions:
- Specificity guides T cell development through a network of ligands.
- The endogenous peptide pool significantly influences T cell development and repertoire formation.
- Altered peptide ligands can function as agonists or antagonists, shaping immune responses.