Document Detail


Human Ly9 (CD229) as novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (B-CLL) recognized by autologous CD8+ T cells.
MedLine Citation:
PMID:  16797413     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: CD229, a cell-surface molecule being involved in cell adhesion, is overexpressed in B-CLL cells. In this study we wanted to explore whether CD229 might function as B-CLL-specific tumor-associated antigen (TAA). PATIENTS AND METHODS: Autologous, CD229-specific HLA-A2-restricted T cells were identified using IFN-gamma-ELISPOT assays and HLA-A2/dimer-peptide staining after 4 weeks of in vitro culture. RESULTS: We were able to expand autologous T cells from 9/11 B-CLL patients using native B-CLL cells as antigen presenting cells (APCs) in 5 cases, whereas for 4 samples an autologous T-cell response could only be evoked by use of CD40L-stimulated B-CLL cells as APCs. The number of CD8+ T cells could be expanded during 4 weeks of in vitro culture with native or CD40L-activated B-CLL cells while the amount of specific T cells recognizing CD229 peptides bound to HLA-A2 dimers increased on average 12-fold (native CLL) and 13-fold (CD40L-activated CLL), respectively. Using IFN-gamma-ELISPOT assays we could demonstrate that the expanded T cells were able to secrete IFN-gamma upon recognition of the antigen. These T cells not only recognized HLA-A0201-binding CD229-derived peptides presented by T2 cells, but also CD229-overexpressing autologous B-CLL cells in an MHC-I-restricted manner. CONCLUSION: In summary, CD229 was shown to be naturally processed and presented as TAA in primary B-CLL cells, enabling the expansion of autologous tumor-specific T cells.
Authors:
Dagmar Bund; Christine Mayr; David M Kofler; Michael Hallek; Clemens-Martin Wendtner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental hematology     Volume:  34     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-26     Completed Date:  2006-08-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  860-9     Citation Subset:  IM    
Affiliation:
KKG Gene Therapy, GSF-National Research Center for Environment and Health, Munich, Germany.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / analysis,  immunology*
CD8-Positive T-Lymphocytes / immunology*
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/LY9 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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