Uncover and compare the human immunopeptidome of Leishmania across the clinical spectrum.

Infection with the Leishmania parasite can lead to a wide spectrum of clinical presentations, ranging from diverse cutaneous presentations (localized, mucocutaneous, disseminated) to a deadly systemic disease (visceral leishmaniasis). Yet, the underlying factors driving this disease spectrum remain mostly unknown. Although Leishmania is an obligatory intracellular parasite surviving in the phagolysosome of key antigen presenting cells, it remains mostly unexplored whether the complex host-parasite interplay translates in an altered net effect on the MHC-presented peptidome to T cells (giving rise to a differential antigen-specific T cell repertoire), and whether and how this is associated with certain disease presentations that have distinct immunopathology patterns. Although attempts were made in murine models, discordant data has often been found between experimental in vivo models, in vitro settings and patients regarding the host immune response after Leishmania infection. By applying a new high-throughput MS-based method on an unique set of patient tissue samples, we aim to perform the first comprehensive screening of the antigenic repertoire and study whether and how this differs between in vitro and in vivo conditions, blood and tissue compartments, and across the clinical presentations.

Keywords:T CYTOTOXIC LYMPHOCYTE

Disciplines:Proteomics, Adaptive immunology, Vaccinology

Project type:Collaboration project