Multiple HLA-A alleles can present an immunodominant peptide of the human melanoma antigen Melan-A/MART-1 to a peptide-specific HLA-A*0201+ cytotoxic T cell line.
The majority of HLA-A*0201-restricted tumor-infiltrating lymphocytes from melanoma patients recognize a peptide, MT(27-35), derived from the Melan-A/MART-1 Ag. This study reports that six variants of HLA-A2 and the HLA-A28 subtype A*6901 can present peptide MT(27-35). A CTL line specific for peptide MT(27-35) was generated by in vitro stimulation of PBL of an HLA-A*0201+, healthy donor with peptide-pulsed, activated autologous B lymphoblasts. This CTL line was shown to recognize peptide MT(27-35) after endogenous processing on Melan-A/MART-1+/HLA-A2+ tumor cells. Moreover, a panel of B lymphoblastoid cell lines (BLCLs) expressing A*0202, A*0204, A*0205, A*0206, A*0209, and with lower efficiency A*6901, could be sensitized to lysis upon incubation with the relevant peptide. As demonstrated by the levels of ED50 and CD8 dependency of lysis, HLA-A*0204 and HLA-A*0205 presented the peptide as efficiently as HLA-A*0201, while the other four alleles were less efficient. Peptide-binding studies suggest that TCR- rather than peptide-binding affinity determines the T cell recognition levels of peptide-pulsed EBV-BLCLs expressing A*0201, A*0204, A*0206, and A*0209. Peptide-pulsed BLCLs expressing HLA-A*0207 or two additional subtypes of HLA-A28 were not recognized. MT(27-35)-specific CTL could also be raised from donors expressing HLA-A*0205. These findings have implications on the applicability of peptide vaccination with peptide MT(27-35) on melanoma patients.
Fleischhauer
K
K
Department of Biology and Biotechnology (DIBIT), H.S. Raffaele Scientific Institute, Milan, Italy.
Tanzarella
S
S
Wallny
H J
HJ
Bordignon
C
C
Traversari
C
C
D000483:Alleles; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D015789:HLA-A2 Antigen / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D058965:MART-1 Antigen; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D009842:Oligopeptides