Identification of HLA-A*0201-restricted T cell epitopes derived from the novel overexpressed tumor antigen calcium-activated chloride channel 2.
Vaccination against tumor Ags may become a promising treatment modality especially in cancer types where other therapeutic approaches fail. However, diversity of tumors requires that a multitude of Ags become available. Differential expression in normal vs cancerous tissues, both at the mRNA and the protein level, may identify Ag candidates. We have previously compared transcripts from squamous cell lung cancer and normal lung tissue using differential display analysis, and found a transcript that was overexpressed in malignant cells and was identical with the calcium-activated chloride channel 2 (CLCA2) gene. We have now selected HLA-A2-restricted peptides from CLCA2, and have generated T cell lines against the CLCA2-derived KLLGNCLPTV, LLGNCLPTV, and SLQALKVTV peptides using in vitro priming. Specificity of T cells was ascertained in ELISPOT assays. The primed T cells also recognized allogeneic tumor cells in an Ag-specific and HLA-restricted fashion. Moreover, peptide LLGNCLPTV was also independently recognized by CD8(+) T cells expanded from pancreatic carcinoma/T cell cocultures. CLCA2-specific CD8(+) T cells were absent from the peripheral blood of healthy donors. These data indicate that an immune response can be induced against CLCA2, which thus may become an important Ag for anti-tumor vaccination approaches.
Konopitzky
Renate
R
Division of Research and Development, Boehringer Ingelheim Austria, Vienna, Austria. renate.konopitzky@vie.boehringer-ingelheim.com
König
Ulrich
U
Meyer
Ralf G
RG
Sommergruber
Wolfgang
W
Wölfel
Thomas
T
Schweighoffer
Tamás
T
D000483:Alleles; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D018118:Chloride Channels / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D015234:HLA-A Antigens / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D009842:Oligopeptides / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology
D000951:Antigens, Neoplasm; C120066:CLCA2 protein, human; D018118:Chloride Channels; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D010446:Peptide Fragments; D002118:Calcium