Human Ly9 (CD229) as novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (B-CLL) recognized by autologous CD8+ T cells.
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.[1]References
- Human Ly9 (CD229) as novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (B-CLL) recognized by autologous CD8+ T cells. Bund, D., Mayr, C., Kofler, D.M., Hallek, M., Wendtner, C.M. Exp. Hematol. (2006) [Pubmed]
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