Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen

Danila Valmori, Frédéric Lévy, Emmanuelle Godefroy, Luigi Scotto, Naira E. Souleimanian, Julia Karbach, Valeria Tosello, Charles S. Hesdorffer, Lloyd J. Old, Elke Jager, Maha Ayyoub

Research output: Contribution to journalArticle

Abstract

Identification of immunodominant CD8+ T cell responses to frequently expressed tumor antigens across MHC class I polymorphism is essential for the implementation of cancer immunotherapy. However, the key factors that determine immunodominance are not fully understood. Because of its frequent expression in tumors and its spontaneous immunogenicity, NY-ESO-1 is a prime target of cancer vaccines and an ideal model antigen for elucidating the molecular basis of immunodominant tumor-specific CD8+ T cell responses. Here, we have assessed CD8+T cell responses to full-length NY-ESO-1 in cancer patients. We identified 3 immunodominant regions of the protein located within 3 distinct clusters of MHC class I binding sequences that co-localize with previously defined clusters of MHC class II binding sequences, are predicted to be hydrophobic and undergo efficient proteasomal processing. Our results support the concept that epitope clustering within defined protein regions identifies tumor antigen immunodominant regions and suggest a general strategy for their identification.

Original languageEnglish (US)
Pages (from-to)163-172
Number of pages10
JournalClinical Immunology
Volume122
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

Fingerprint

Immunodominant Epitopes
Neoplasm Antigens
Cluster Analysis
Epitopes
T-Lymphocytes
Neoplasms
Cancer Vaccines
Immunotherapy
Proteins
Antigens

Keywords

  • Cancer testis antigens
  • CTL
  • Human
  • Immunodominance
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Valmori, D., Lévy, F., Godefroy, E., Scotto, L., Souleimanian, N. E., Karbach, J., ... Ayyoub, M. (2007). Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen. Clinical Immunology, 122(2), 163-172. https://doi.org/10.1016/j.clim.2006.09.005

Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen. / Valmori, Danila; Lévy, Frédéric; Godefroy, Emmanuelle; Scotto, Luigi; Souleimanian, Naira E.; Karbach, Julia; Tosello, Valeria; Hesdorffer, Charles S.; Old, Lloyd J.; Jager, Elke; Ayyoub, Maha.

In: Clinical Immunology, Vol. 122, No. 2, 02.2007, p. 163-172.

Research output: Contribution to journalArticle

Valmori, D, Lévy, F, Godefroy, E, Scotto, L, Souleimanian, NE, Karbach, J, Tosello, V, Hesdorffer, CS, Old, LJ, Jager, E & Ayyoub, M 2007, 'Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen', Clinical Immunology, vol. 122, no. 2, pp. 163-172. https://doi.org/10.1016/j.clim.2006.09.005
Valmori, Danila ; Lévy, Frédéric ; Godefroy, Emmanuelle ; Scotto, Luigi ; Souleimanian, Naira E. ; Karbach, Julia ; Tosello, Valeria ; Hesdorffer, Charles S. ; Old, Lloyd J. ; Jager, Elke ; Ayyoub, Maha. / Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen. In: Clinical Immunology. 2007 ; Vol. 122, No. 2. pp. 163-172.
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