The dominant repertoire of minor histocompatibility antigens

Abstract

Patients undergoing allogeneic stem cell transplantation (alloSCT) as treatment for hematological diseases face the risk of Graft-versus-Host Disease (GvHD as well as relapse. Minor histocompatibility antigens (MiHAs) are essential targets after allogeneic stem cell transplantation (alloSCT). MiHAs are polymorphic T-cell epitopes that differ between patients and donors due to genetic differences, and are presented on healthy as well as malignant patient cells. T cells targeting broadly expressed MiHAs induce Graft-versus-Leukemia (GvL) reactivity as well as GvHD, while T cells for MiHAs with restricted or preferential expression on hematopoietic or non-hematopoietic cells may skew responses towards GvL or GvHD, respectively. MiHAs are relevant to predict, monitor and manipulate clinical responses to minimize GvHD and maximize GvL reactivity. This thesis describes an optimized strategy using genome-wide association scanning to identify MiHAs, explores the identified expanded MiHA repertoire also in regards to their potential as immunotherapeutic targets, and analyzes MiHA-specific T-cell frequencies after donor lymphocyte infusion following alloSCT using DNA-barcoded multimers as well as T-cell receptor analysis.