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MHC-I antigen processing and presentation
The proteasome is the core of the ubiquitin-proteasome system and responsible for the degradation of the majority of the protein in the cytosol. It is therefore involved in a large variety of metabolic pathways, including inflammation and antigen processing and presentation (APP). The proteasome is only the first step of the APP pathway. We investigate APP steps and how they impinge upon the recognition by CD8+ T cells.
Proteasome-catalysed peptide splicing
Proteasome produces fragments by canonical peptide-bond hydrolysis or by peptide splicing. Indeed, proteasome can break a protein and reshuffle its sequence by combining non-continuous fragments, thereby generating spliced peptides. By peptide splicing, proteasome significantly enlarges the antigenic landscape of a cell. We developed a novel method for spliced peptide identification and discovered its relevance in the antigen presentation.
Extracellular proteasome
The proteasome is active also in the extracellular space where it can cleave osteopontin and release peptides that promote cell migration. We showed evidence that this mechanism could play a role in multiple sclerosis.
Proteasome isoforms
There are several proteasome isoforms, which carry out preferential functions in different cell types. We investigate the biochemistry behind their function.