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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2014
Author Keck Simone, Schmaler Mathias, Ganter Stefan, Wyss Lena, Oberle Susanne, Huseby Eric S, Zehn Dietmar, King Carolyn G,
Project The role of TCR affinity in CD4+ T cell asymmetric division and differentiation
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Original article (peer-reviewed)

Journal Proceedings of the National Academy of Sciences of the United States of America
Volume (Issue) 111(41)
Page(s) 14852 - 7
Title of proceedings Proceedings of the National Academy of Sciences of the United States of America
DOI 10.1073/pnas.1403271111


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.