Analogues of CTL epitopes with improved MHC class-I binding capacity elicit anti-melanoma CTL recognizing the wild-type epitope

Int J Cancer. 1997 Jan 27;70(3):302-9. doi: 10.1002/(sici)1097-0215(19970127)70:3<302::aid-ijc10>;2-h.


The MHC class-I binding affinity of an epitope is an important parameter determining the immunogenicity of the peptide-MHC complex. In order to improve the immunogenicity of an epitope derived from melanocyte lineage-specific antigen gp100, we performed amino-acid substitutions within the epitope and assayed both HLA-A*0201 binding and CTL recognition. Anchor replacements towards the HLA-A*0201 peptide-binding motif gave rise to peptides with higher HLA-A*0201 binding capacity compared to the wild-type epitope. In addition, several of the gp100 154-162 epitope-analogues were more efficient at target-cell sensitization for lysis by anti-gp100 154-162 CTL compared to the wild-type epitope. These altered gp100 154-162 epitopes were subsequently tested for their capacity to induce CTL responses in vivo using HLA-A*0201/Kb transgenic mice, and in vitro using HLA-A*0201 + donor-derived lymphocytes. Interestingly, the peptide-specific CTL obtained, which were raised against the different gp100 154-162 epitope-analogues, displayed cross-reactivity with target cells endogenously processing and presenting the native epitope. These data demonstrate that altered epitopes can be exploited to elicit native epitope-reactive CTL. The use of epitope-analogues with improved immunogenicity may contribute to the development of CTL-epitope based vaccines in viral disease and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cross Reactions / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-DQ Antigens / immunology*
  • HLA-DQ alpha-Chains
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / immunology*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured
  • gp100 Melanoma Antigen


  • Epitopes, T-Lymphocyte
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQA1 antigen
  • Histocompatibility Antigens Class I
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Pmel protein, mouse
  • gp100 Melanoma Antigen