1. Identification of phosphatidylinositol 4-kinase type II [beta] as HLA class II-restricted target in graft versus leukemia reactivity
- Author
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Griffioen, Marieke, van der Meijden, Edith D., Slager, Elisabeth H., Honders, M. Willy, Rutten, Caroline E., van Luxemburg-Heijs, Simone A.P., von dem Borne, Peter A., van Rood, Johannes J., Willemze, Roel, and Falkenburg, J.H. Frederik
- Subjects
Immunotherapy -- Research ,Leukemia -- Care and treatment ,Lymphocytes -- Properties ,Stem cells -- Transplantation ,Stem cells -- Research ,Phosphotransferases -- Properties ,HLA class II antigens -- Properties ,Science and technology - Abstract
Patients with hematological malignancies can be successfully treated with HLA-matched T cell-depleted allogeneic stem cell transplantation (alIoSCT) and subsequent donor lymphocyte infusions (DLIs). The efficacy of DLI is mediated by donor T cells recognizing minor histocompatibility antigens (mHags) on malignant recipient cells. Because HLA class II molecules are predominantly expressed on hematopoietic cells, mHag-specific [CD4.sup.+] T cells may selectively mediate graft versus leukemia (GvL) reactivity without graft versus host disease (GvHD). In this study, we used a recombinant bacteria cDNA library for the identification of the first autosomal HLA class II (HLA-DQBl*0603)-restricted mHag LBPI4K2B-1S encoded by the broadly expressed phosphatidylinositol 4-kinase type II [beta] gene. A polyclonal [CD4.sup.+] T cell response against LB-PI4K2B-1S was demonstrated in a patient with relapsed chronic myeloid leukemia (CML) who responded to DLI after HLA-matched alIoSCT. LB-PI4K2B-1S-specific [CD4.sup.+] T cells recognized and lysed the [CD34.sup.+] CML cells of the patient and other leukemic cells as well as high HLA-DQ-expressing normal hematopoietic cells. HLA-DQ expression on normal cells of nonhematopoietic origin was moderately up-regulated by IFN-[gamma], and not sufficient for T cell recognition. We hypothesize that LB-PI4K2B-1S-specific [CD4.sup.+] T cells contributed to the antitumor response by both directly eliminating malignant cells as effector cells and stimulating [CD8.sup.+] T cell immunity as helper cells. donor lymphocyte infusions | hematological malignancies | immunotherapy | stem cell transplantation | T lymphocytes
- Published
- 2008