Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of patients with NY-ESO-1-expressing melanoma.
NY-ESO-1 is a member of the cancer-testis family of tumor antigens that elicits strong humoral and cellular immune responses in patients with NY-ESO-1-expressing cancers. Since CD4(+) T lymphocytes play a critical role in generating antigen-specific cytotoxic T lymphocyte and antibody responses, we searched for NY-ESO-1 epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules. Autologous monocyte-derived dendritic cells of cancer patients were incubated with recombinant NY-ESO-1 protein and used in enzyme-linked immunospot (ELISPOT) assays to detect NY-ESO-1-specific CD4(+) T lymphocyte responses. To identify possible epitopes presented by distinct HLA class II alleles, overlapping 18-mer peptides derived from NY-ESO-1 were synthetized and tested for recognition by CD4(+) T lymphocytes in autologous settings. We identified three NY-ESO-1-derived peptides presented by DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of two melanoma patients sharing these HLA class II alleles. Specificity of recognition was confirmed by proliferation assays. The characterization of HLA class II-restricted epitopes will be useful for the assessment of spontaneous and vaccine-induced immune responses of cancer patients against defined tumor antigens. Further, the therapeutic efficacy of active immunization using antigenic HLA class I-restricted peptides may be improved by adding HLA class II-presented epitopes.
Jäger
E
E
Medizinische Klinik II, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany. 100333.1434@compuserve.com
Jäger
D
D
Karbach
J
J
Chen
Y T
YT
Ritter
G
G
Nagata
Y
Y
Gnjatic
S
S
Stockert
E
E
Arand
M
M
Old
L J
LJ
Knuth
A
A
D000483:Alleles; D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D059845:HLA-DRB4 Chains; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D006684:HLA-DR Antigens; D059845:HLA-DRB4 Chains; D008565:Membrane Proteins; D011506:Proteins; D011994:Recombinant Proteins