Abstract
How follicular helper T cells (T(FH) 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 (CD62L(hi)CCR7(hi)) from CXCR5(lo) 'emigrant' effector helper T cells and CXCR5(hi) 'resident' T(FH) cells expressing the transcriptional repressor Bcl-6 (CD62L(lo)CCR7(lo)). 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 T(FH) 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 T(FH) function in vivo.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Adoptive Transfer
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Cell Differentiation / immunology
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Cytokines / biosynthesis
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism
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Histocompatibility Antigens Class II / metabolism
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L-Selectin / immunology
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Lymph Nodes / immunology
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Mice
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Mice, Transgenic
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Positive Regulatory Domain I-Binding Factor 1
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Proto-Oncogene Proteins c-bcl-6
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Antigen, T-Cell / metabolism
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T-Box Domain Proteins / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Helper-Inducer / transplantation
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Transcription Factors / biosynthesis
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Transcription Factors / immunology
Substances
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Adjuvants, Immunologic
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Bcl6 protein, mouse
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Cytokines
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DNA-Binding Proteins
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Histocompatibility Antigens Class II
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Prdm1 protein, mouse
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Proto-Oncogene Proteins c-bcl-6
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Receptors, Antigen, T-Cell
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Transcription Factors
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L-Selectin
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Positive Regulatory Domain I-Binding Factor 1