Exploring antigen presentation and T cell recognition in leishmaniasis

Leishmaniasis, caused by parasites of the genus Leishmania, is one of the most severe vector-borne parasitic diseases. The global burden is substantial and it is currently endemic in 99 countries spanning multiple continents. The primary disease spectrum ranges from the non-lethal but disfiguring skin disease cutaneous leishmaniasis (CL), to visceral leishmaniasis (VL), which is fatal without treatment and affects the visceral organs responsible for priming of T and B cell immunity (e.g. spleen, bone marrow, lymph nodes). A long line of work has shown that immunity to Leishmania is predominantly T cell-mediated. T-cell mediated immunity relies on the presentation of Leishmania antigens by Major Histocompatibility Complex (MHC) molecules on antigen-presenting cells to a cognate T cell receptor (TCRs) on a T cell. While broad characteristics of the T cell response have been described, such as a T helper 1 response being protective in animal models, nothing is known on which Leishmania antigens actually get presented to a given cognate TCR by which particular MHC molecule. In this thesis, I thus explore the role of T cell antigen presentation and recognition in the disease outcome of leishmaniasis, irrespective of clinical form, and also in the context of a complex chronic co-infection with HIV. More specifically, I elucidated which particular MHC’s may be involved in leishmaniasis disease outcome, and which Leishmania antigens get MHC-presented in a natural disease setting in humans.