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The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding

Nature Immunology volume 10, pages 375–384 (2009)Cite this article

An Addendum to this article was published on 21 March 2011

This article has been updated

Abstract

How follicular helper T cells (TFH cells) differentiate to regulate B cell immunity is critical for effective protein vaccination. Here we define three transcription factor T-bet–expressing antigen-specific effector helper T cell subsets with distinguishable function, migratory properties and developmental programming in vivo. Expression of the transcriptional repressor Blimp-1 distinguished T zone 'lymphoid' effector helper T cells (CD62LhiCCR7hi) from CXCR5lo 'emigrant' effector helper T cells and CXCR5hi 'resident' TFH cells expressing the transcriptional repressor Bcl-6 (CD62LloCCR7lo). We then show by adoptive transfer and intact polyclonal responses that helper T cells with the highest specific binding of peptide–major histocompatibility complex class II and the most restricted T cell antigen receptor junctional diversity 'preferentially' developed into the antigen-specific effector TFH compartment. Our studies demonstrate a central function for differences in the binding strength of the T cell antigen receptor in the antigen-specific mechanisms that 'program' specialized effector TFH function in vivo.

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Figure 1: Three subsets of antigen-specific effector helper T cells emerge in draining lymph nodes.
Figure 2: Lymphoid effector helper T cells express Blimp-1.
Figure 3: 'Resident' effector TFH cells express Bcl-6.
Figure 4: Precursors with high-affinity TCR 'preferentially' develop into 'resident' TFH cells.
Figure 5: 'Resident' TFH cells have stronger pMHCII binding than do other effector helper T cells.
Figure 6: 'Resident' TFH cells express a more restricted TCR repertoire than do other effector helper T cells.
Figure 7: 'Resident' TFH cells 'preferentially' develop after priming with adjuvants that promote high-affinity antigen-specific helper T cells.

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Change history

  • 08 March 2009

    NOTE: In the version of this article initially published online, CD62L is identified incorrectly as a chemokine. The correct definition should be 'L-selectin'. The error has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

Supported by the National Institutes of Health (AI047231, AI040215 and AI059475 to M.G.M.-W.). This is manuscript 19762 from The Scripps Research Institute.

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Authors and Affiliations

  1. Department of Immunology and Microbial Sciences, La Jolla, California, USA

    Nicolas Fazilleau, Louise J McHeyzer-Williams & Michael G McHeyzer-Williams

  2. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA

    Hugh Rosen

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Contributions

N.F., L.J.M.-W. and M.G.M.-W. designed experiments; N.F. did experiments and analyzed data; N.F., L.J.M.-W. and M.G.M.-W. wrote the manuscript; and H.R. consulted on AAL-R experiments and provided necessary reagents.

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Correspondence to Michael G McHeyzer-Williams.

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Fazilleau, N., McHeyzer-Williams, L., Rosen, H. et al. The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat Immunol 10, 375–384 (2009). https://doi.org/10.1038/ni.1704

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