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Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation.

  • Keck S Laboratory of Transplantation Immunology, and.
  • Schmaler M Laboratory of Immunoregulation, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland;
  • Ganter S Laboratory of Transplantation Immunology, and.
  • Wyss L Laboratory of Transplantation Immunology, and.
  • Oberle S Swiss Vaccine Research Institute, and Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland; and.
  • Huseby ES Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655.
  • Zehn D Swiss Vaccine Research Institute, and Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland; and.
  • King CG Laboratory of Transplantation Immunology, and carolyn.king@unibas.ch.
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  • 2014-10-01
Published in:
  • Proceedings of the National Academy of Sciences of the United States of America. - 2014
follicular helper
infection
lymphocytes
Animals
Antigens
B-Lymphocytes
CD4-Positive T-Lymphocytes
Cell Differentiation
Cell Proliferation
Dose-Response Relationship, Immunologic
Immunologic Memory
Interleukin-2
Ligands
Lymphocyte Activation
Major Histocompatibility Complex
Mice
Receptors, Antigen, T-Cell
Th1 Cells
English 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.
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  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/91873
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