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.