New strategies in identification and quantification of minor histocompatibility antigens

Abstract

The involvement of Minor histocompatibility antigens (MiHA) in the graft versus tumor is described about three decades ago. Nowadays, there are many evidences that, after HLA-matched allogeneic hematopoietic stem cell transplantation (HSCT) MiHA specific T cells mediate both graft versus leukemia (GVL) reactivity and graft versus host disease (GVHD), which is a major cause of morbidity and mortality. To identify MiHA we decided to establish a new strategy based on the bone fide eluted ligandome. Then we developed a database dedicated for identification of polymorphic peptides called human short peptide variation database (HSPVdb). To identify potential MiHA among the huge number of polymorphic peptides eluted from HLA-A*0201 or HLA-B*0702 we selected the top 25 MiHA candidates identified in chapter 2. From this set of data we could validate 2 novel potential MiHA being (LB-CLYBL-1Y & LB-TEP1-1S). To find out at which stages the great_est losses occurred, we developed a method to be able to quantitate MiHA on the cell surface. In addition we studied the phenomenon of the unidirectional T cell responses against MiHA. We studied in depth the presentation of non-canonical long peptides in HLA-A*0201 molecules.