title: Revisiting thymic positive selection and the mature T cell repertoire for antigen.
abstract: To support effective host defense, the T cell repertoire must balance breadth of recognition with sensitivity for antigen. The concept that T lymphocytes are positively selected in the thymus is well established, but how this selection achieves such a repertoire has not been resolved. Here we suggest that it is direct linkage between self and foreign antigen recognition that produces the necessary blend of TCR diversity and specificity in the mature peripheral repertoire, enabling responses to a broad universe of unpredictable antigens while maintaining an adequate number of highly sensitive T cells in a population of limited size. Our analysis also helps to explain how diversity and frequency of antigen-reactive cells in a T cell repertoire are adjusted in animals of vastly different size scale to enable effective antipathogen responses and suggests a possible binary architecture in the TCR repertoire that is divided between germline-related optimal binding and diverse recognition.
authors.affiliation: Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: Vrisekoop
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: João P
authors.initials: JP
authors.lastname: Monteiro
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: mandlj@niaid.nih.gov.
authors.forename: Judith N
authors.initials: JN
authors.lastname: Mandl
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: rgermain@nih.gov.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta