A direct comparison of cytolytic T-lymphocyte responses to Melan-A peptides in vitro: differential immunogenicity of Melan-A27-35 and Melan-A26-35.
In this study we directly compared the in vitro responses of T-cells from normal donors and melanoma patients to Melan-A27-35 and Melan-A26-35. These peptides have been previously used in peptide-based vaccination studies. Following three stimulations with peptide-pulsed antigen-presenting cells in vitro, Melan-A-specific cytolytic T-lymphocytes (CTLs) were generated from seven of 20 subjects; two of the seven subjects responded reproducibly to both Melan-A27-35 and Melan-A26-35, three to only Melan-A27-35 and two to only Melan-A26-35. However, CTLs generated with either Melan-A27-35 or Melan-A26-35 showed cross recognition, and both types of CTL could recognize naturally processed antigen displayed on HLA-A2+ tumour cells. Furthermore, Melan-A-specific CTLs could also be generated by stimulating peripheral blood mononuclear cells with autologous melanoma cells. Our results suggest that some subjects may have a bias in their CTL repertoire which favours the generation of Melan-A27-35 specific CTLs, while others may favour Melan-A26-35 specific CTLs. It is also likely that CTL precursors capable of detecting both peptides may have different affinities to the two Melan-A peptides. Since it is difficult to predict the CTL responses to Melan-A peptide in a given individual, we suggest vaccinating with both Melan-A27-35 and Melan-A26-35 peptides in clinical trials.
Chen
Q
Q
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Austin Repat Cancer Centre, Heidelberg, VIC, Australia. qiyuan.chen@ludwig.edu.au
Jackson
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H
Cebon
J
J
Gibbs
P
P
Davis
I D
ID
Trapani
J A
JA
D019496:Cancer Vaccines / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; C105787:MART-1-Melan-A(27-35) epitope; D009363:Neoplasm Proteins; D010446:Peptide Fragments