Identification of a naturally processed NY-ESO-1 peptide recognized by CD8+ T cells in the context of HLA-B51.
NY-ESO-1 is one of the most immunogenic cancer antigens known to date, inducing humoral and cellular immune responses in a high proportion of patients with advanced NY-ESO-1-expressing cancers. The assessment of spontaneous and vaccine-induced CD8+ T cell responses has been limited to a small number of known NY-ESO-1 epitopes presented by MHC class I alleles. Recently, a new method to monitor NY-ESO-1-specific CD8+ T cell responses was introduced that does not depend on the individual MHC class I status and on predefined peptide epitopes. Antigen-presenting cells transduced with recombinant adenoviral vectors encoding NY-ESO-1 were used to stimulate CD8+ selected NY-ESO-1-specific T cells. Effector cells were tested for recognition of autologous B cell targets transfected with NY-ESO-1 using a recombinant vaccinia virus construct. Using a modified approach we identified the NY-ESO-1 p94-102 peptide as being recognized by CD8+ T cells in the context of HLA- B51. NY-ESO-1 p94-102 specific CD8+ T cells recognized naturally processed NY-ESO-1 presented by HLA-B51+ monocyte-derived dendritic and tumor cells. Transfection of target cells with NY-ESO-1 combined with different HLA class I alleles confirmed that the NY-ESO-1 peptide was naturally processed and recognized by HLA-B51-restricted CD8+ T cell lines and clones. Therefore, NY-ESO-1 p94-102 is a new candidate peptide antigen for cancer immunotherapy and for the monitoring of spontaneous and vaccine-induced NY-ESO-1-specific T cell responses in HLA- B51+ patients with NY-ESO-1 expressing malignancies.
II. Medizinische Klinik, Hämatologie - Onkologie, Krankenhaus Nordwest, Frankfurt, Germany. elke.jaeger@licr.org
Elke
E
Jäger
Julia
J
Karbach
Sacha
S
Gnjatic
Dirk
D
Jäger
Markus
M
Maeurer
Akin
A
Atmaca
Michael
M
Arand
Jonathan
J
Skipper
Elisabeth
E
Stockert
Yao-Tseng
YT
Chen
Lloyd J
LJ
Old
Alexander
A
Knuth
D000256:Adenoviridae / Q000235:genetics; D000912:Antibodies, Neoplasm / Q000097:blood; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005822:Genetic Vectors; D015235:HLA-B Antigens / Q000276:immunology*; D059949:HLA-B51 Antigen; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; D008565:Membrane Proteins; D010455:Peptides; D011506:Proteins