title: Growth inhibition of clonogenic leukemic precursor cells by minor histocompatibility antigen-specific cytotoxic T lymphocytes.
abstract: Minor histocompatibility (mH) antigens appear to play a major role in bone marrow transplantation (BMT) using HLA-identical donors. Previously, we reported the isolation of major histocompatibility complex (MHC)-restricted mH antigen-specific cytotoxic T lymphocytes (CTL) from patients with graft-vs.-host disease or rejection after HLA-identical BMT. We have demonstrated that mH antigens can be recognized on hematopoietic progenitor cells, and residual recipient CTL specific for mH antigens expressed on donor hematopoietic progenitor cells may be responsible for graft rejection in spite of intensive conditioning regimens in HLA-identical BMT. Here, we investigated whether mH antigen-specific CTL directed against the mH antigens HA-1 to HA-5 and the male-specific antigen H-Y were capable of antigen-specific inhibition of in vitro growth of clonogenic leukemic precursor cells. We demonstrate that mH antigen-specific CTL against all mH antigens tested can lyse freshly obtained myeloid leukemic cells, that these mH antigen-specific CTL can inhibit their clonogenic leukemic growth in vitro, and that this recognition is MHC restricted. We illustrate that leukemic (precursor) cells can escape elimination by mH antigen-specific CTL by impaired expression of the relevant MHC restriction molecule. We suggest that mH antigen-specific MHC-restricted CTL may be involved in vivo in the graft-vs.-leukemia reactivity after BMT.
authors.affiliation: Department Hematology, University Medical Center, Leiden, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: H M
authors.initials: HM
authors.lastname: Goselink
authors.forename: D
authors.initials: D
authors.lastname: van der Harst
authors.forename: S A
authors.initials: SA
authors.lastname: van Luxemburg-Heijs
authors.forename: Y M
authors.initials: YM
authors.lastname: Kooy-Winkelaar
authors.forename: L M
authors.initials: LM
authors.lastname: Faber
authors.forename: J
authors.initials: J
authors.lastname: de Kroon
authors.forename: A
authors.initials: A
authors.lastname: Brand
authors.forename: W E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: R
authors.initials: R
authors.lastname: Willemze
mesh_terms: D000208:Acute Disease; D016026:Bone Marrow Transplantation / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006086:Graft vs Host Disease; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000601:surgery; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000601:surgery; D008285:Major Histocompatibility Complex; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015778:Minor Histocompatibility Antigens