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Identification of phosphatidylinositol 4-kinase type II β as HLA class II-restricted target in graft versus leukemia reactivity.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 3/11/2008, Vol. 105 Issue 10, p3837-3842. 6p. 5 Graphs. - Publication Year :
- 2008
-
Abstract
- Patients with hematological malignancies can be successfully treated with HLA-matched T cell-depleted allogeneic stem cell transplantation (alloSCT) 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+ 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-DQB1*0603)-restricted mHag LB-PI4K2B-1S encoded by the broadly expressed phosphatidylinositol 4-kinase type II β gene. A polyclonal CD4+ T cell response against LB-Pl4K2B-1S was demonstrated in a patient with relapsed chronic myeloid leukemia (CML) who responded to DLI after HLA-matched alloSCT. LB-PI4K2B-1S-specific CD4+ T cells recognized and lysed the CD344 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-γ and not sufficient for T cell recognition. We hypothesize that LB-PI4K2B-1S-specific CD4+ T cells contributed to the antitumor response by both directly eliminating malignant cells as effector cells and stimulating CD8+ T cell immunity as helper cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HEMATOLOGY
*PHOSPHOINOSITIDES
*FOCAL adhesion kinase
*LYMPHOCYTES
LEUKEMIA genetics
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 105
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 31503041
- Full Text :
- https://doi.org/10.1073/pnas.0712250105