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Analogues of CTL epitopes with improved MHC class‐I binding capacity elicit anti‐melanoma CTL recognizing the wild‐type epitope
Author(s) -
Bakker Alexander B.H.,
van der Burg Sjoerd H.,
Huijbens Richard J.F.,
Drufhout JanWouter,
Melief Cornelis J.M.,
Adema Gosse J.,
Figdor Carl G.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970127)70:3<302::aid-ijc10>3.0.co;2-h
Subject(s) - epitope , ctl* , immunogenicity , biology , major histocompatibility complex , linear epitope , mhc class i , antigen , microbiology and biotechnology , virology , immunology , cd8
The MHC class‐1 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 gp 100, 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/K b transgenic mice, and in vitro using HLA‐A*0201 + donor‐derived lymphocytes. Interestingly, the peptide‐specific CTL obtained, which were raised against the different gp 100 154–162 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. Int. J. Cancer , 70:302–309, 1997. © 1997 Wiley‐Liss, Inc.