Journal Article

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

Fazilleau, Nicolas, McHeyzer-Williams, Michael G, McHeyzer-Williams, Louise J, Rosen, Hugh

2009

Overview

Efficient humoral immunity requires B cell–T cell interactions in lymphoid follicles. McHeyzer-Williams and colleagues show that CXCR5 + follicular helper T cells have T cell antigen receptors with higher affinity for antigen than do other responding effector helper T cells. 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 .

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Adjuvants, Immunologic - pharmacology / Adoptive Transfer / Animals / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / Biomedical and Life Sciences / Biomedicine / Cell Differentiation - immunology / Cell receptors / Cytokines - biosynthesis / DNA-Binding Proteins - immunology / DNA-Binding Proteins - metabolism / Histocompatibility Antigens Class II - metabolism / Immunology / Infectious Diseases / L-Selectin - immunology / Lymph Nodes - immunology / Mice / Mice, Transgenic / Physiological aspects / Positive Regulatory Domain I-Binding Factor 1 / Protein binding / Proto-Oncogene Proteins c-bcl-6 / Receptors, Antigen, T-Cell - immunology / Receptors, Antigen, T-Cell - metabolism / T cells / T-bet Transcription Factor / T-Box Domain Proteins - metabolism / T-Lymphocyte Subsets - immunology / T-Lymphocyte Subsets - metabolism / T-Lymphocytes, Helper-Inducer - immunology / T-Lymphocytes, Helper-Inducer - metabolism / T-Lymphocytes, Helper-Inducer - transplantation / Transcription Factors - biosynthesis / Transcription Factors - immunology