HLA class II-restricted recognition of common tumor epitopes on human melanoma cells by CD4+ melanoma-infiltrating lymphocytes.
CD4+ T cell clones derived from lymphocytes infiltrating four human melanomas specifically recognized melanoma-derived tumor epitopes as shown by secretion of tumor necrosis factor (TNF) in vitro upon interaction with autologous melanoma cells, whereas they did not recognize HLA class II-expressing autologous lymphoblasts or HLA class II mismatched allogeneic melanoma cells. Specificity was further established by demonstrating that TNF responses to tumor cells were inhibited by HLA-DR or HLA-DQ monoclonal antibodies. Most of these clones cross-reacted with allogeneic melanoma cells expressing a potentially restricting HLA allele or a structurally similar one. These data show that shared epitopes of human melanoma cells presented on HLA class II molecules are frequently recognized by autologous CD4+ T lymphocytes.
Le Dréan
E
E
Unité INSERM 211, Nantes, France.
Gervois
N
N
Diez
E
E
Semana
G
G
Dreno
B
B
Jotereau
F
F
D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002417:Cattle; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008545:Melanoma / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006681:HLA-D Antigens; D008233:Lymphotoxin-alpha