title: T cells survey the stability of the self: a testable hypothesis on the homeostatic role of TCR-MHC interactions.
abstract: In the lifetime of an individual, every single gene will have undergone mutation on about 10(10) separate occasions. Nevertheless, cancer occurs mainly with advancing age. Here, we hypothesize that the evolutionary pressure driving the creation of the T cell receptor (TCR) repertoire was primarily the homeostatic surveillance of the genome. The subtly variable T cells may in fact constitute an evolutionary link between the invariable innate and hypervariable B cell systems. The new model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected TCR and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. Notwithstanding, the 'homeostatic role of T cells' model offers a more realistic explanation as to how a naïve clonal immune system can cope with the much faster replicating pathogens, despite a limited repertoire that is capable of facing only a small fraction of the vast antigenic universe at a time.
authors.affiliation: Department of Probability, Alfred Rényi Institute of Mathematics, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Bakács
authors.forename: Jitendra N
authors.initials: JN
authors.lastname: Mehrishi
authors.forename: Tamás
authors.initials: T
authors.lastname: Szabados
authors.forename: László
authors.initials: L
authors.lastname: Varga
authors.forename: Miklós
authors.initials: M
authors.lastname: Szabó
authors.forename: Gábor
authors.initials: G
authors.lastname: Tusnády
mesh_terms: D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D019143:Evolution, Molecular; D006706:Homeostasis; D006801:Humans; D007239:Infections / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell