Identification of NY-ESO-1 peptide analogues capable of improved stimulation of tumor-reactive CTL Journal Article


Authors: Chen, J. L.; Dunbar, P. R.; Gileadi, U.; J├Ąger, E.; Gnjatic, S.; Nagata, Y.; Stockert, E.; Panicali, D. L.; Chen, Y. T.; Knuth, A.; Old, L. J.; Cerundolo, V.
Article Title: Identification of NY-ESO-1 peptide analogues capable of improved stimulation of tumor-reactive CTL
Abstract: Expression of NY-ESO-1 in a high proportion of different human tumors makes this protein a very attractive vaccine target. NY-ESO-1 peptides, recognized by HLA-A2-restricted CTL, have recently been described. However, it remains unclear how efficiently tumors generate these epitopes, and whether peptide analogues can be used for optimal expansion and activation of NY-ESO-1-specific HLA-A2-restricted CTL. By generating CTL clones, we demonstrate that NY-ESO-1-positive tumor cells are efficiently killed by HLA- A2-restricted CTL specific for the peptide epitope NY-ESO-1 157-165. Presentation of this epitope is not affected by the presence or absence of the proteasome subunits low molecular proteins 2 and 7 and is not blocked by proteasome inhibitors, while it is impaired in the TAP-deficient cell line LBL 721.174. NY-ESO-1 157-165 peptide analogues were compared for their antigenicity and immunogenicity using PBL from melanoma patients. Three peptides, containing the carboxyl-terminal cysteine substituted for either valine, isoleucine, or leucine, were recognized at least 100 times more efficiently than the wild-type peptide by specific CTL. Peptide analogues were capable of stimulating the expansion of NY-ESO-1-specific CTL from PBL of melanoma patients much more efficiently than wild-type peptide. These findings define the processing requirements for the generation of the NY-ESO- 1 157-165 epitope. Identification of highly antigenic NY-ESO-1 peptide analogues may be important for the development of vaccines capable of expanding NY-ESO-1-specific CTL in cancer patients.
Keywords: human cell; antigen expression; proteins; melanoma; proteasome; proteasome inhibitor; amino acid substitution; protein binding; membrane proteins; tumor cells, cultured; tumor antigen; antigen presentation; lymphocyte activation; antigens, neoplasm; antigen specificity; immunogenicity; hla antigen class 2; antigen recognition; lymphocyte clone; peptide fragments; vaccination; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; cytotoxicity, immunologic; epitopes, t-lymphocyte; t lymphocyte activation; cysteine; cell killing; hla-a2 antigen; peptide derivative; antigenicity; humans; human; priority journal; article; intracellular fluid
Journal Title: Journal of Immunology
Volume: 165
Issue: 2
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2000-07-15
Start Page: 948
End Page: 955
Language: English
PUBMED: 10878370
PROVIDER: scopus
DOI: 10.4049/jimmunol.165.2.948
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Yasuhiro Nagata
    11 Nagata
  2. Sacha Gnjatic
    111 Gnjatic
  3. Lloyd J Old
    386 Old