In summary, we have analyzed and pinpointed the structural basis for Bl-Eng2 engagement of Dectin-2 during vaccine priming, and demonstrated that these interactions augment the development of antigen-specific CD4+ and CD8+ T cell responses with phenotypic, functional, and localization features designed to promote resistance against inhaled fungal and viral infections at the respiratory mucosa. Here, CD4 is linked to viral infectious disease.