Hematopoietic lineage-restricted minor histocompatibility antigen HA-1 in graft-versus-leukemia activity after donor lymphocyte infusion

J Immunother. 2004 Mar-Apr;27(2):156-60. doi: 10.1097/00002371-200403000-00009.

Abstract

Immunocompetent alloreactive donor lymphocytes directed against minor histocompatibility antigens are supposed to be responsible for graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) activity after allogeneic stem cell transplantation. The authors describe the detection of HA-1-specific T cells by peptide-loaded dimers and flow cytometry in the peripheral blood of a patient in complete remission but without GvHD after donor lymphocyte infusion for chemotherapy-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia. The HA-1-specific T cells were sorted and an alloreactive, polyclonal T-cell line with specific lytic activity against HA-1-positive target cells, including leukemic cells, was established. Although P190 bcr/abl peptide-specific CD8positive T cells were detected in the peripheral blood at the same time, these T cells could not be expanded. Furthermore, no P190 bcr/abl peptide-specific T-cell response could be induced in vitro, even when peptide-loaded dendritic cells were used as stimulator cells. The authors conclude that in the absence of GvHD, HA-1-specific rather than P190 bcr/abl-specific T cells are responsible for ongoing GvL activity.

MeSH terms

  • Cell Division
  • Cell Lineage*
  • Cell Transplantation*
  • Dendritic Cells / cytology
  • Dimerization
  • Flow Cytometry
  • Graft vs Leukemia Effect*
  • HLA-A Antigens / chemistry*
  • HLA-A2 Antigen
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Immunotherapy / methods*
  • Leukemia / therapy*
  • Lymphocytes / cytology*
  • Minor Histocompatibility Antigens / immunology*
  • Oligopeptides
  • Peptides / chemistry
  • Phenotype
  • Protein Binding
  • T-Lymphocytes / metabolism

Substances

  • HA-1 antigen
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Minor Histocompatibility Antigens
  • Oligopeptides
  • Peptides