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Related Experiment Videos

Positive selection is limited by available peptide-dependent MHC conformations.

H E Stefanski1, S C Jameson, K A Hogquist

  • 1Department of Laboratory Medicine, University of Minnesota, Minneapolis, MN 55455, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|March 22, 2000
PubMed
Summary

The diversity of self peptides presented in the thymus is crucial for developing a varied T cell repertoire. This study identified specific peptides that can correct a known "hole" in the T cell repertoire by restoring positive selection.

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Area of Science:

  • Immunology
  • Molecular Biology
  • T cell biology

Background:

  • T cell repertoire diversity is shaped by self peptides presented during thymic development.
  • A specific defect in T cell response (H-2K-restricted response to OVA in bm8 mice) was previously observed.
  • This defect, termed a 'hole in the immunological repertoire', suggested a potential absence of a critical selecting self peptide.

Purpose of the Study:

  • To investigate if the 'hole in the immunological repertoire' in bm8 mice is due to the lack of a specific self peptide.
  • To identify peptides capable of restoring positive selection of T cells in bm8 mice.
  • To understand the role of self peptides in shaping T cell receptor diversity and MHC molecule conformation.

Main Methods:

  • Utilized established criteria for identifying positive selection ligands.

Related Experiment Videos

  • Tested for the restoration of positive selection of OT-I transgenic T cells (OVA-specific, H-2K-restricted) in bm8 mice using identified peptides.
  • Analyzed the effect of peptides on MHC (H-2K) conformation using MHC-specific antibodies.

    • Main Results:

    • Identified specific peptides that restored positive selection of OT-I thymocytes in bm8 mice.
    • Demonstrated that the T cell repertoire can be limited by the requirement for specific self peptides during thymic development.
    • Showed that peptides can influence MHC conformation, affecting ligand diversity both directly and indirectly.

    Conclusions:

    • Self peptide diversity is essential for selecting a broad range of T cells.
    • The absence of specific self peptides can create 'holes' in the T cell repertoire.
    • Peptides play a dual role in T cell selection by varying side chains and modulating MHC conformation.