Anaphylaxis is a type of severe allergic reaction that is initiated by cross-linking of high-affinity IgE on mast cells leading to mast cell degranulation. Recent evidence demonstrates that T follicular helper cells (Tfh) producing both IL-4 and IL-13, termed Tfh13s, are necessary for the generation of anaphylactic IgE. The mechanisms regulating the polarization of these T cells, however, remain unclear. Parasite infection, which induces strong IgE responses, fails to induce Tfh13 polarization. We therefore hypothesized that papain, a cysteine protease that resembles parasitic CA family peptidases, would similarly fail to induce Tfh13 polarization compared to the aeroallergen Alternaria due to differential action on dendritic cells (DCs). We found that intranasal immunization with LPS+OVA and Alternaria+OVA induced a 2-fold Tfh expansion in the draining lymph node compared to papain+OVA. Additionally, Alternaria stimulated Tfh13 polarization and high-affinity IgE production while papain only induced Th2 responses and non-specific IgE. Analysis of DC migration by immunization with fluorescently tagged OVA alongside these adjuvants revealed markedly different migration kinetics following each stimulus. However, numbers of Ag⁺ DCs, amount of antigen uptake, and proportions of Ag⁺ migratory vs. resident DCs in the mediastinal lymph nodes were similar between all groups. Thus, we demonstrate that papain, in contrast to Alternaria, is unable to induce Tfh13 polarization and anaphylactic IgE. We propose that the differential effects of these adjuvants are likely mediated by alternative mechanisms of DC licensing and distinct DC transcriptional profiles.

J Immunol May 1, 2020, 204 (1 Supplement) 66.19;