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Identification of phosphatidylinositol 4-kinase type II [beta] as HLA class II-restricted target in graft versus leukemia reactivity
- Source :
- Proceedings of the National Academy of Sciences of the United States. March 11, 2008, Vol. 105 Issue 10, p3837, 6 p.
- Publication Year :
- 2008
-
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
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 105
- Issue :
- 10
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.177816746