Identification of Subdominant CTL Epitopes of the GP100 Melanoma-Associated Tumor Antigen by Primary in Vitro Immunization with Peptide-Pulsed Dendritic Cells

Van Tsai, Scott Southwood, John Sidney, Kazuyasu Sakaguchi, Yutaka Kawakami, Ettore Appella, Alessandro Sette, Esteban Celis

Research output: Contribution to journalArticle

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Abstract

The gp100 melanoma-associated tumor Ag was selected as a model system to study the diversity of human antitumor cytotoxic T cell responses. First, peptides corresponding to dominant gp100 HLA-A2.1-restricted CTL epitopes were tested using lymphocytes from normal volunteers and an in vitro priming protocol that uses peptide-pulsed dendritic cells as APCs and IL-7 and IL-10 as immune-enhancing cytokines. High CTL activity toward both peptide-pulsed target cells and gp100+ melanoma cells was obtained with four out of five peptides tested. Second, HLA-A2.1-binding peptides from gp100 that do no appear to represent CTL epitopes in melanoma patients were also tested for their capacity to induce CTL using the in vitro priming protocol. Three of six peptides tested induced CTL in lymphocytes from normal volunteers. One of these peptides was also immunogenic for lymphocytes derived from a melanoma patient in remission. Because these three CTL epitopes were not recognized in the natural immune response in melanoma patients but do appear as immunogens when peptides are used to induce the T cell response, they may be considered as typical "subdominant" epitopes. The results are discussed in the context of the usefulness of this approach to detail the immunologic potential of a given tumor-associated Ag and its relevance for the design of effective immune-based therapies.

Original languageEnglish (US)
Pages (from-to)1796-1802
Number of pages7
JournalJournal of Immunology
Volume158
Issue number4
StatePublished - Feb 15 1997
Externally publishedYes

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gp100 Melanoma Antigen
Neoplasm Antigens
Dendritic Cells
Epitopes
Immunization
Peptides
Melanoma
Lymphocytes
Healthy Volunteers
T-Lymphocytes
Interleukin-7
In Vitro Techniques
Interleukin-10
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Identification of Subdominant CTL Epitopes of the GP100 Melanoma-Associated Tumor Antigen by Primary in Vitro Immunization with Peptide-Pulsed Dendritic Cells. / Tsai, Van; Southwood, Scott; Sidney, John; Sakaguchi, Kazuyasu; Kawakami, Yutaka; Appella, Ettore; Sette, Alessandro; Celis, Esteban.

In: Journal of Immunology, Vol. 158, No. 4, 15.02.1997, p. 1796-1802.

Research output: Contribution to journalArticle

Tsai, Van ; Southwood, Scott ; Sidney, John ; Sakaguchi, Kazuyasu ; Kawakami, Yutaka ; Appella, Ettore ; Sette, Alessandro ; Celis, Esteban. / Identification of Subdominant CTL Epitopes of the GP100 Melanoma-Associated Tumor Antigen by Primary in Vitro Immunization with Peptide-Pulsed Dendritic Cells. In: Journal of Immunology. 1997 ; Vol. 158, No. 4. pp. 1796-1802.
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