Étude de la présentation d'antigènes de classe I : compréhension des mécanismes d'épissage peptidique sur base de l'étude de l'apprêtement d'antigènes tumoraux épissés par les 4 sous-types de protéasome

By tying peptides originally distant in parental proteins, the proteasome can generate spliced peptides recognized by cytolytic T cells. Here, we study the production of six tumor-associated spliced peptides by the four proteasome subtypes: the standard proteasome (SP), the immunoproteasome (IP) and the intermediate proteasomes β5i (SIP) and β1iβ5i (DIP). Three of these peptides are better produced by SP while the other three are better produced by IP and DIP. The current model suggests that the production of a spliced peptide depends on the abundance of splice partners. Surprisingly, we have found that the efficiency of the peptide splicing reaction also appears to rely on the affinity of the nucleophilic peptide for the "prime" site of the catalytic subunit. In a second part of this work, we try to identify the peptide recognized by an anti-tumor CTL and which is presented in the absence of the TAP transporter.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202