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Tolerance and determinant hierarchy

S C Schneider1, H K Deng, B Rottinger

  • 1Department of Microbiology and Molecular Genetics, UCLA, USA.

Novartis Foundation Symposium
|October 7, 1998
PubMed
Summary
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Antigen-presenting cells (APCs) shape T cell responses by controlling which antigen determinants are displayed. This study reveals how APC processing influences determinant selection and tolerance induction in mice.

Area of Science:

  • Immunology
  • T cell biology
  • Antigen presentation

Background:

  • T cell responses are directed against specific determinants on antigens.
  • Antigen-presenting cells (APCs) critically influence T cell recognition by processing and displaying these determinants.
  • The thymus and peripheral APCs shape the T cell repertoire and response selection.

Purpose of the Study:

  • To investigate how the hierarchy of determinant display by APCs affects tolerance induction.
  • To analyze the role of antigen processing machinery in shaping determinant display on MHC class II molecules.

Main Methods:

  • Studied transgenic mice with varying serum levels of hen egg lysozyme.
  • Analyzed determinant display hierarchy and its impact on tolerance.
  • Investigated proteolysis and disulfide bond reduction in antigen processing.

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Main Results:

  • APC processing influences the selection of determinants presented to T cells.
  • The hierarchy of determinant display impacts the induction of tolerance to specific determinants.
  • Proteolysis and disulfide bond reduction are key factors in shaping determinant presentation.

Conclusions:

  • APC processing and determinant display hierarchy are crucial for shaping T cell repertoire and immune responses.
  • Understanding these mechanisms is vital for controlling immune tolerance and reactivity.