title: Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation.
abstract: Cumulative T-cell receptor signal strength and ensuing T-cell responses are affected by both antigen affinity and antigen dose. Here we examined the distinct contributions of these parameters to CD4 T-cell differentiation during infection. We found that high antigen affinity positively correlates with T helper (Th)1 differentiation at both high and low doses of antigen. In contrast, follicular helper T cell (TFH) effectors are generated after priming with high, intermediate, and low affinity ligand. Unexpectedly, memory T cells generated after priming with very low affinity antigen remain impaired in their ability to generate secondary Th1 effectors, despite being recalled with high affinity antigen. These data challenge the view that only strongly stimulated CD4 T cells are capable of differentiating into the TFH and memory T-cell compartments and reveal that differential strength of stimulation during primary T-cell activation imprints unique and long lasting T-cell differentiation programs.
authors.affiliation: Laboratory of Transplantation Immunology, and.
authors.forename: Simone
authors.initials: S
authors.lastname: Keck
authors.affiliation: Laboratory of Immunoregulation, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland;
authors.forename: Mathias
authors.initials: M
authors.lastname: Schmaler
authors.affiliation: Laboratory of Transplantation Immunology, and.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ganter
authors.affiliation: Laboratory of Transplantation Immunology, and.
authors.forename: Lena
authors.initials: L
authors.lastname: Wyss
authors.affiliation: Swiss Vaccine Research Institute, and Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland; and.
authors.forename: Susanne
authors.initials: S
authors.lastname: Oberle
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Huseby
authors.affiliation: Swiss Vaccine Research Institute, and Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland; and.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.affiliation: Laboratory of Transplantation Immunology, and carolyn.king@unibas.ch.
authors.forename: Carolyn G
authors.initials: CG
authors.lastname: King
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D004306:Dose-Response Relationship, Immunologic; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000941:Antigens; D007376:Interleukin-2; D008024:Ligands; D011948:Receptors, Antigen, T-Cell
keywords: follicular helper; infection; lymphocytes