Nicky de Vrij Poster 2024

Mr Nicky de Vrij

Institute of Tropical Medicine Antwerp, Belgium

The Human Immunopeptidome of Cutaneous Leishmaniasis Across the Clinical Spectrum: New Targets for Vaccine Design?

Poster Abstract

Infection with Leishmania can lead to a spectrum of clinical manifestations with distinct immunopathology, ranging from self-healing cutaneous lesions to a deadly systemic disease, depending primarily on the infecting parasite species. However, certain Leishmania species can cause more than one clinical presentation. For example, the species L. aethiopica can cause three different forms of cutaneous leishmaniasis (localized, mucocutaneous, and diffuse). Although Leishmania is an obligatory intracellular parasite that resides in the phagolysosome of key antigen-presenting cells, it remains unexplored whether and how differences in antigen presentation relate to the diversity of clinical presentations. For instance, small genomic differences between parasite strains, or host susceptibility factors, are likely to translate in an altered net effect on antigen presentation, skewing the balance between protective immunity and disease susceptibility. Therefore, we hypothesize that differential antigen presentation may underlie the development of different clinical presentations of leishmaniasis. Understanding whether and how differential antigen presentation can lead to selfhealing or difficult-to-treat CL is crucial to elucidate protective immunity to Leishmania, and identifying antigens correlated with protective immunity can lead to more rational vaccine design. Thus, we have performed the first comprehensive screening of the Leishmania immunopeptidome in humans, using mass spectrometry-based immunopeptidomics and Oxford Nanopore Technologies sequencing-based human leukocyte antigen genotyping on a unique set of 27 L. aethiopica-infected patient tissue samples (9 LCL, 14 MCL, 4 DCL). Currently, all experiments have been finished, and a first batch of 18 samples has already resulted in the identification of 115 Leishmania immunopeptides. The analyses of a second batch are ongoing, and expected to finish in time for the VALIDATE annual.  

Biography

Nicky is a PhD fellow at the Clinical Immunology unit of the Institute of Tropical Medicine in Antwerp and the Adrem Data Lab of the UAntwerp. He focuses on the T cell-driven immunity observed in leishmaniasis, and the entire process of T cell antigen presentation and recognition. By coupling high-throughput and high-resolution wet lab techniques with bioinformatics, he generates insights on pMHC-TCR interactions in leishmaniasis. During his PhD, Nicky has gained ample experience in single-cell RNA and T cell receptor sequencing data analysis, and mass spectrometry-based immunopeptidomics. He also set up a Human Leukocyte Antigen sequencing pipeline, using Oxford Nanopore Technologies sequencers. In the context of capacity building, he has implemented a pipeline at the University of Gondar in Ethiopia, and trained several local researchers to perform this routinely.