Foreignness as a matter of degree: the relative immunogenicity of peptide/MHC ligands.
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.
Interdisciplinary Programme for Cellular Regulation, Mathematics Institute, University of Warwick, Coventry CV4 7AL, UK. hugo@maths.warwick.ac.uk
Hugo A
HA
van den Berg
David A
DA
Rand
D000951:Antigens, Neoplasm / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D001324:Autoantigens