Identification of 4 novel HLA-B*40:01 restricted minor histocompatibility antigens and their potential as targets for graft-versus-leukemia reactivity.

Background: Patients with hematologic malignancies can be successfully treated with donor lymphocyte infusion after HLA-matched allogeneic hematopoietic stem cell transplantation. The effect of donor lymphocyte infusion is mediated by donor T cells recognizing minor histocompatibility antigens. T cells recognizing hematopoietic restricted minor histocompatibility antigens may induce selective graft-versus-leukemia reactivity, whereas broadly-expressed antigens may be targeted in graft-versus-host disease.

High-throughput characterization of 10 new minor histocompatibility antigens by whole genome association scanning.

Patients with malignant diseases can be effectively treated with allogeneic hematopoietic stem cell transplantation (allo-SCT). Polymorphic peptides presented in HLA molecules, the so-called minor histocompatibility antigens (MiHA), play a crucial role in antitumor immunity as targets for alloreactive donor T cells. Identification of multiple MiHAs is essential to understand and manipulate the development of clinical responses after allo-SCT.

Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have emerged as a promising tool for clinical application. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more important, display immunosuppressive capacities. These properties may be of therapeutic value in allogeneic transplantation to prevent graft rejection and to prevent and treat graft-versus-host disease.

Proteosomal degradation of BCR/ABL protein can generate an HLA-A*0301-restricted peptide, but high-avidity T cells recognizing this leukemia-specific antigen were not demonstrated.

Background And Objectives: Cytotoxic T-lymphocytes (CTL) have been generated in vitro against chronic myeloid leukemia (CML)-associated BCR/ABL-specific peptides. We analyzed the existence of high-avidity T cells recognizing endogenously processed BCR/ABL-specific proteins.

Design And Methods: We performed binding studies of BCR/ABL-specific peptides, proteosomal digestion of BCR/ABL breakpoint overlapping protein, mass spectrometry of eluates from HLA-*0301-transduced K562 cells, and tried to isolate peptide-specific T-cells using tetramers.