Characterization of antigenic peptides presented by HLA-B44 molecules on tumor cells expressing the gene MAGE-3.

Fleischhauer, K;Fruci, D;Van Endert, P;Herman, J;Traversari, C;et.al.
(1996) International Journal of Cancer — Vol. 68, n° 5, p. 622-628 (1996)

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Authors
  • Fleischhauer, K
    Author
  • Fruci, D
    Author
  • Van Endert, P
    Author
  • Herman, J
    Author
  • Author
  • Traversari, C
    Author
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Abstract
The amino acid sequence of the protein encoded by the gene MAGE-3 was screened for peptides containing the binding motif for HLA-B44. Nine peptides were synthesized, and their binding affinity for HLA-B*4402 and -B*4403 was analyzed in an HLA class I alpha-chain refolding assay. Four peptides with binding affinity for HLA-B*4403 were chosen for in vitro cytotoxic T-lymphocyte induction assays using as antigen-presenting cells peptide-pulsed, autologous activated B lymphoblasts from a healthy, B*4403+ donor. Peptide-specific effectors could be raised only against one peptide, M3-167. Cytotoxic T lymphocytes specific for this peptide were also able to recognize melanoma cell lines expressing HLA-B44 and the gene MAGE-3, strongly suggesting that M3-167 is a naturally processed MAGE-3-encoded epitope presented by HLA-B44. M3-167 is a I amino acid N-terminal extension of M3-168, a naturally processed epitope MAGE-3-encoded epitope presented by HLA-A1 that has been previously described. TAP binding studies of these 2 peptides revealed that the TAP affinity of M3-167 is about 9-fold higher than that of M3-168. M3-167 or a longer precursor could be transported into the endoplasmatic reticulum, where it could be trimmed for presentation by HLA-A1 or -B44 molecules. Taken together, our data suggest that M3-167 could be an immunodominant peptide encoded by the gene MAGE-3.
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Citations

Fleischhauer, K., Fruci, D., Van Endert, P., Herman, J., Tanzarella, S., Wallny, H. J., Coulie, P., Bordignon, C., & Traversari, C. (1996). Characterization of antigenic peptides presented by HLA-B44 molecules on tumor cells expressing the gene MAGE-3. International Journal of Cancer, 68(5), 622-628. https://doi.org/10.1002/(SICI)1097-0215(19961127)68:5<622::AID-IJC12>3.0.CO;2-3 (Original work published 1996)