Identification of a persistent Ascaris-derived Kalirin epitope associated with chronic T cell activation in the lung.

Ascariasis remains a dominant global health burden due to its vast prevalence and associated morbidity. The obligatory migration of Ascaris larvae through pulmonary tissue triggers intense type-2 inflammation which typically presents as acute allergic airway disease. Even after the parasite is eliminated, a single episode of larval migration can result in chronic lung damage and dysfunction, which may be driven by the long-term retention of helminth antigens in macrophages. However, the molecular identity of these retained antigens, and the mechanisms by which they sustain chronic T cell responses, remain unknown. In this study, we utilized immunopeptidomics to identify a retained peptide specific from Ascaris that is sequestered and presented by pulmonary macrophages via MHC-II. We further demonstrated that this retained peptide serves as an epitope which is associated with the development of specific T helper cell populations that persist long after the infection has cleared. These findings define a potential molecular mechanism for persistent helminth-induced immune cell activiation in the lungs and identify a retained epitope as a potential contributor to the development of chronic pulmonary inflammation following parasite elimination from the lungs.