Assessment of immunogenicity of human melan-A peptide analogues in HLA-A*0201/K-b transgenic mice

Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides MelanA(27-35) and Melan-A(26-35) greatly improved their binding and the stability of peptide/HLA-A*0201 comp lexes. In particular, one Melan-A peptide analogue was more efficient in th e generation of Melan-A peptide-specific and melanoma-reactive CTL than its parental peptide in vitro from human PDL. In this study, we analyzed the i n vivo immunogenicity of Melan-A natural peptides and their analogues in HL A-A*0201/K-b transgenic mice. We found that two human Melan-A natural pepti des, Melan-A(26-35) and Melan-A(27-35), were relatively weak immunogens, wh ereas several Melan-A peptide analogues were potent immunogens for in vivo CTL priming. In addition, induced Melan-A peptide-specific mouse CTL cross- recognized natural Melan-A peptides and their analogues. More interestingly , these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner. Our results indicate that the HLA-A*0201/K-b transgenic mouse is a useful animal model to perfor m preclinical testing of potential cancer vaccines, and that Melan-A peptid e analogues are attractive candidates for melanoma immunotherapy.