The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding.
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.
Fazilleau
Nicolas
N
Department of Immunology and Microbial Sciences, La Jolla, California, USA.
McHeyzer-Williams
Louise J
LJ
Rosen
Hugh
H
McHeyzer-Williams
Michael G
MG
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D000098815:T-bet Transcription Factor
D000276:Adjuvants, Immunologic; C490010:Bcl6 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C513258:Prdm1 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D011948:Receptors, Antigen, T-Cell; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D019041:L-Selectin; D000074462:Positive Regulatory Domain I-Binding Factor 1