Y. Men et al., Assessment of immunogenicity of human melan-A peptide analogues in HLA-A*0201/K-b transgenic mice, J IMMUNOL, 162(6), 1999, pp. 3566-3573
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.