2007 Fiscal Year Final Research Report Summary
Induction of cytotoxic T lymphocytes specific for minor histocompatility antigen through transferringThell receptor gene
| Project/Area Number |
18591049
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kanazawa University |
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Principal Investigator |
TAKAMI Akiyoshi Kanazawa University, University Hospital, Associate Professor (80324078)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Yukio Kanazawa University, University Hospital, Assistant Professor (10322116)
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| Project Period (FY) |
2006 – 2007
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| Keywords | minor histocompatibility antigen / leukemia / stem cell transplantation |
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| Research Abstract |
In hematopoietic SCT from HLA-matched donors, allogeneic immune reactions such as GVHD and GVL effect are induced by disparities in minor histocompatibility antigens (mHas) between donor and recipient. CD62L has been reported to act as an mHa based on analysis of the outcome of allogeneic SCT. To identify peptides derived from CD62L that may be involved in GVL effect, we prepared all possible 18 different 9-mer peptides derived from CD62L that include codon 213 in one of the 9 positions, and tested for cytotoxic T-cell precursors specific to any of these peptides in patients after CD62L-disparate SCT. PBMC obtained from 5 patients with I-ILA-A*2402 who developed GVHD following transplantation were incubated with autologous monocyte-derived DCs or HLA-A*2402-transfected T2 cells which were pulsed with the 9-mer peptides, or incubated with the peptides only, and 1FN-gamma secretion from PBMC after 16 hours incubation was examined. Two to 4 different recipient-type peptides for each patient induced higher IFN-gamma secretion than the others. By stimulating PBMC with the peptide-pulsed T2-A24 cells, T-cell lines specific for 4 peptides were obtained. The cultured T cells efficiently lysed peptide-pulsed T2-A24 cells as well as HLA-A*2402-positive lymphoblastic cell line cells that were disparate with CD62L. Addition of mAbs against HLA-class I blocked this cytotoxicity. WIC stabilization assay demonstrated that the 4 peptides bound to the cell surface and HLA complex stabilized. These results suggest these peptides may serve as mHas capable of inducing GVL effect, and CTLs recognizing CD62L-derived polymorphic peptides may have therapeutic value in treating relapsed leukemia after SCT.
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