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

The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding.
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DOI:
10.1038/ni.1704
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发表时间:
2009-04
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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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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