Endoglucanase-2 (Eng2), a conserved immunodominant antigen in dimorphic fungi that elicits immunity and resistance during infection

Abstract

Herein, we describe a conserved surface and cell wall protein, Endoglucanase 2 (Eng2), expressed on the etiological agents that cause the endemic systemic mycoses of North America - Blastomyces, Coccidioides and Histoplasma . We demonstrate that despite sequence variation of the protein across these related fungi, exposure to Eng2 vaccinates and protects inbred and humanized HLA-DR4 strains of mice against lethal experimental infections with these fungi by eliciting adaptive immunity mediated by CD4 T cells. We also show that CD4 T cell precursors against Eng2 are detectable in naïve individuals and that patients who have recovered from these infections evince a memory and recall CD4 T cell response to Eng2 and its immunodominant epitopes that we have mapped. We create and catalogue new tools and information such as immunodominant peptide epitopes of Eng2 from each fungus recognized by inbred mice and human subjects and we engineer novel peptide-MHC II tetramers for tracking T cells in inbred and HLA-DR4 humanized mice that will be useful for those who study these infections in mice and humans. Lastly, because most patients demonstrate memory and recall responses against Eng2, our work oRers new tools for diagnosis of this collection of infectious diseases across North America.