Alternative antigen processing and presentation pathways by tumors

The study of immunity against Transporter Associated with Antigen Processing (TAP)-deficient cells led to the discovery of peptides presented by such TAP-deficient cells. Some of these peptides constituted antigens to Cytotoxic T-lymphocytes (CTL) and these CTL only recognized TAP-deficient cells but not normal cells. These peptides were called “T-cell epitopes associated with impaired peptide processing” (TEIPP). Therefore, TEIPP corresponds to immunogenic peptides that are presented only in cases of processing deficiency and not by normal cells. The studies of TEIPP antigens thus far have revealed that these antigens are promising candidates for the combat of immune escaped tumors. However, several aspects about TEIPPs needed clarification: what are the processing pathways that lead to generation and presentation of TEIPP antigens; what is the mechanism behind the immunogenicity of TEIPP; what are the charac teristics of TEIPP peptides presented by non-classical Major Histocompatibility Complex class I (MHC-I) molecules. The studies presented in this thesis are focused on these topics