Identification of two Melan-A CD4+ T cell epitopes presented by frequently expressed MHC class II alleles.
Because of its expression pattern restricted to cells of the melanocytic lineage and to melanoma cells, Melan-A is an important target of immunotherapeutic approaches for the treatment of melanoma. Identification of Melan-A derived sequences recognized by specific T cells is therefore of great interest for the development of these therapeutic strategies. Using circulating CD4(+) T cells from healthy donors, we identified two Melan-A-derived CD4(+) T cell epitopes mapping to the 1-20 and 91-110 regions of the protein and restricted by HLA-DR11 and HLA-DR52 molecules, respectively. CD4(+) T cells specific for the identified epitopes were able to recognize the native antigen when endogenously expressed by antigen presenting cells and tumor cells. In addition, CD4(+) T cells specific for Melan-A 91-110 recognized the epitope after exogenous processing and presentation of Melan-A recombinant protein. Identification of these epitopes will be instrumental for the evaluation of the immune response to Melan-A in cancer patients.
Godefroy
Emmanuelle
E
Ludwig Institute Clinical Trial Center, Division of Medical Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, 650 West 168th Street, Black Building Room 20-09, New York, NY 10032, USA.
Scotto
Luigi
L
Souleimanian
Naira E
NE
Ritter
Gerd
G
Old
Lloyd J
LJ
Jotereau
Francine
F
Valmori
Danila
D
Ayyoub
Maha
M
D000483:Alleles; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D059810:HLA-DR Serological Subtypes; D015805:HLA-DR5 Antigen / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D010449:Peptide Mapping
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D015805:HLA-DR5 Antigen; D000949:Histocompatibility Antigens Class II; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins