Foreignness as a matter of degree: the relative immunogenicity of peptide/MHC ligands

J Theor Biol. 2004 Dec 21;231(4):535-48. doi: 10.1016/j.jtbi.2004.07.008.

Abstract

The ability of T lymphocytes (T cells) to recognize and attack foreign invaders while leaving healthy cells unharmed is often analysed as a discrete self/non-self dichotomy, with each peptide/MHC ligand classified as either self or non-self. We argue that the ligand immunogenicity is more naturally treated as a continuous quantity, and show how to define and quantitate relative ligand immunogenicity. In our theory, self-tolerance is acquired through reduction of the relative immunogenicity of autoantigens, whereas xenoantigens, typically not presented during induction of deletional tolerance, retain a high degree of relative immunogenicity. Autoantigens that are not prominently presented in deletional tolerance likewise retain a high relative immunogenicity and remain essentially foreign. According to our analysis, any given autoantigen can attain a high level of relative immunogenicity, provided it is presented at sufficiently high levels. Our theory provides a quantitative tool to analyse the immunogenicity of tumour-associated neoantigens and the aetiology of autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Autoantigens / immunology*
  • Autoimmunity
  • Humans
  • Immune Tolerance
  • Immunity, Innate
  • Models, Immunological*
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Neoplasm
  • Autoantigens