T cell activation plays a central role in immune response and in the maintenance of self-tolerance. We analyzed the evolutionary history of Tcell regulatory molecules. Nine genes involved in triggering Tcell activation or in regulating the ensuing response evolved adaptively in mammals. Several positively selected sites overlap with positions interacting with the binding partner or with cellular components. Population genetic analysis in humans revealed acomplex scenario of local (FASLG, CD40LG, HAVCR2) and worldwide (FAS, ICOSLG) adaptation and H.sapiens-to-Neandertal gene flow (gene transfer between populations). Disease variants in these genes are preferential targets of pathogen-driven selection, and a Crohn's disease risk polymorphism targeted by bacterial. -driven selection modulates the expression of ICOSLG in response to a bacterial superantigen. Therefore, we used evolutionary information to generate experimentally testable hypotheses concerning the function of specific genetic variants and indicate that adaptation to infection underlies the maintenance of autoimmune risk alleles. © 2013 Elsevier Inc.

Forni, D., Cagliani, R., Pozzoli, U., Colleoni, M., Riva, S., Biasin, M., et al. (2013). A 175 Million Year History of T Cell Regulatory Molecules Reveals Widespread Selection, with Adaptive Evolution of Disease Alleles. IMMUNITY, 38(6), 1129-1141 [10.1016/j.immuni.2013.04.008].

A 175 Million Year History of T Cell Regulatory Molecules Reveals Widespread Selection, with Adaptive Evolution of Disease Alleles

FILIPPI, GIULIA;DE GIOIA, LUCA;Sironi, M.
2013

Abstract

T cell activation plays a central role in immune response and in the maintenance of self-tolerance. We analyzed the evolutionary history of Tcell regulatory molecules. Nine genes involved in triggering Tcell activation or in regulating the ensuing response evolved adaptively in mammals. Several positively selected sites overlap with positions interacting with the binding partner or with cellular components. Population genetic analysis in humans revealed acomplex scenario of local (FASLG, CD40LG, HAVCR2) and worldwide (FAS, ICOSLG) adaptation and H.sapiens-to-Neandertal gene flow (gene transfer between populations). Disease variants in these genes are preferential targets of pathogen-driven selection, and a Crohn's disease risk polymorphism targeted by bacterial. -driven selection modulates the expression of ICOSLG in response to a bacterial superantigen. Therefore, we used evolutionary information to generate experimentally testable hypotheses concerning the function of specific genetic variants and indicate that adaptation to infection underlies the maintenance of autoimmune risk alleles. © 2013 Elsevier Inc.
Articolo in rivista - Articolo scientifico
Adaptation, Physiological; Alleles; Animals; Autoimmune Diseases; Biological Evolution; Gene Flow; Genetic Predisposition to Disease; Genetics, Population; Humans; Lymphocyte Activation; Neanderthals; Polymorphism, Single Nucleotide; Programmed Cell Death 1 Receptor; Risk; Selection, Genetic; Self Tolerance; T-Lymphocytes, Regulatory; Immunology and Allergy; Infectious Diseases; Immunology
English
2013
38
6
1129
1141
none
Forni, D., Cagliani, R., Pozzoli, U., Colleoni, M., Riva, S., Biasin, M., et al. (2013). A 175 Million Year History of T Cell Regulatory Molecules Reveals Widespread Selection, with Adaptive Evolution of Disease Alleles. IMMUNITY, 38(6), 1129-1141 [10.1016/j.immuni.2013.04.008].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/66398
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