Abstract
We describe here a shared 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 vaccinated and protected 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 were detectable in naive individuals and that patients who had recovered from these infections evinced a memory and recall CD4+ T cell response to Eng2 and its immunodominant epitopes that we have mapped. We created and cataloged new tools and information, such as immunodominant peptide epitopes of Eng2 from each fungus recognized by inbred mice and humans, and we engineered peptide-MHC II tetramers to track T cells in inbred and HLA-DR4-humanized mice. These tools and tetramers will be useful for those who study these infections in mice and humans. Last, because most patients demonstrated immune memory and recall responses against Eng2, our work offers tools for the diagnosis of this collection of infectious diseases across North America.