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Related Experiment Videos

Endogenous altered peptide ligands can affect peripheral T cell responses

K Vidal1, B L Hsu, C B Williams

  • 1Center for Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.

The Journal of Experimental Medicine
|April 1, 1996
PubMed
Summary

Peripheral T cells ignore low levels of self-antigens. However, increased self-antigen presentation can cause T cell antagonism, influencing T cell responses and selection.

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Area of Science:

  • Immunology
  • T cell biology
  • Self-antigen recognition

Background:

  • T cells encounter numerous self-peptide/MHC ligands in the thymus and periphery.
  • Endogenous ligands are crucial for T cell selection in the thymus.
  • The impact of endogenous ligands on peripheral T cells remains unclear.

Purpose of the Study:

  • To investigate the direct effects of endogenously synthesized altered peptide ligand (APL)/MHC complexes on peripheral T cells.
  • To determine the threshold of self-antigen presentation required to elicit a response in peripheral T cells.

Main Methods:

  • Utilized a transgenic mouse model with a reversed antigen system (Ser69 agonist, Hbd(64-76) APL).
  • Assessed T cell responses to varying levels of endogenous Hbd(64-76)/I-Ek complexes presented by antigen-presenting cells (APCs).

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  • Examined the influence of CD4 coreceptor levels on T cell responses.

    • Main Results:

    • Constitutive levels of endogenous Hbd(64-76)/I-Ek complexes were insufficient to impact Ser69-reactive T cells.
    • Elevated expression of Hbd(64-76)/I-Ek complexes by APCs induced T cell antagonism in primary T cells and hybridomas.
    • CD4 coreceptor levels modulated the response pattern to endogenous Hbd(64-76)/I-Ek ligands.

    Conclusions:

    • Peripheral T cells are selected to tolerate constitutive levels of endogenous self-antigen complexes.
    • Endogenous APLs can influence peripheral T cell responses under specific conditions that alter TCR/ligand interaction efficacy.
    • Endogenous APLs play a role in both thymic T cell selection and peripheral T cell responses.