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Related Experiment Videos

Thymic selection does not limit the individual MHC diversity.

José A M Borghans1, André J Noest, Rob J De Boer

  • 1Theoretical Biology, Utrecht University, Utrecht, The Netherlands. J.Borghans@sanquin.nl

European Journal of Immunology
|November 25, 2003
PubMed
Summary
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The number of major histocompatibility (MHC) molecules in individuals doesn't follow the expected trade-off. Mathematical modeling suggests higher MHC diversity enhances T cell repertoire size and pathogen resistance.

Area of Science:

  • Immunology
  • Computational Biology
  • Evolutionary Biology

Background:

  • Major histocompatibility (MHC) molecules are crucial for immune response.
  • Individual MHC diversity is thought to balance pathogen detection and self-tolerance.

Purpose of the Study:

  • To investigate the relationship between MHC molecule diversity and T cell repertoire size.
  • To challenge the traditional trade-off hypothesis regarding MHC expression.

Main Methods:

  • Development and analysis of a mathematical model.
  • Incorporation of experimental parameter estimates for negative and positive selection.

Main Results:

  • The traditional trade-off model fails to explain observed MHC diversity (around 10-20 types).

Related Experiment Videos

  • Increased MHC diversity enhances the number of positively selected T cell clones.
  • The functional T cell repertoire size increases with MHC diversity up to over 100 types.
  • Pathogen resistance only decreases at unrealistically high MHC diversities (>1,500 types).

    • Conclusions:

    • The number of MHC molecules expressed per individual is not solely dictated by a simple trade-off.
    • Higher MHC diversity may be beneficial for expanding the T cell repertoire and improving pathogen resistance.