CD23 is recognized as tumor-associated antigen (TAA) in B-CLL by CD8+ autologous T lymphocytes.
OBJECTIVE
CD23 is constitutively and atypically expressed on malignant B cells in patients with chronic lymphocytic leukemia (B-CLL). Here, we investigated whether CD23-derived peptides might function as B-CLL-specific tumor-associated antigen (TAA).


METHODS
Using IFN-gamma-ELISPOT assays and HLA-A2/dimer-peptide staining we identified autologous, CD23-specific HLA-A0201-restricted T cells after 4 weeks of in vitro culture.


RESULTS
We were able to expand autologous T cells from 8/11 B-CLL patients by using native and CD40L-activated B-CLL cells as antigen-presenting cells (APCs) in 5 cases whereas for 3 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. We could demonstrate that the expanded T cells were also able to secrete IFN-gamma upon recognition of the antigen using IFN-gamma-ELISPOT assays. Furthermore, these T cells not only recognized HLA-A0201-binding CD23-derived peptides presented by T2 cells, but also CD23-overexpressing autologous B-CLL cells in an MHC-I-restricted manner.


CONCLUSIONS
In sum, CD23-derived peptides were shown to be naturally processed and presented as TAA in primary B-CLL, enabling the expansion of autologous tumor-specific T cells.
Bund
Dagmar
D
KKG Gene Therapy, GSF-National Research Center for Environment and Health, Munich, Germany.
Mayr
Christine
C
Kofler
David M
DM
Hallek
Michael
M
Wendtner
Clemens-Martin
CM
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000473:pathology; D000951:Antigens, Neoplasm / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020014:K562 Cells; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology*
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D017455:Receptors, IgE; D023201:CD40 Ligand; D007371:Interferon-gamma