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Differential gene expression profiles in a human T-cell line stimulated with a tumor-associated self-peptide versus an enhancer agonist peptide.
Clin Cancer Res. 2003 May; 9(5):1616-27.CC

Abstract

PURPOSE

Previous studies have shown that a specific 9-mer amino acid epitope (designated CAP-1) of the human "self" tumor-associated carcinoembryonic antigen can be used to stimulate CD8+ T cells from peripheral blood mononuclear cells of carcinoma patients vaccinated with pox vector-based carcinoembryonic antigen vaccines. A T-cell receptor agonist epitope of CAP-1 (designated CAP1-6D) has been shown to enhance the stimulation of T cells over levels obtained using CAP-1. The purpose of this study was to analyze gene expression profiles in T cells stimulated with the native CAP-1 versus the agonist CAP1-6D peptide.

EXPERIMENTAL DESIGN

Microarray analyses were conducted to analyze differential gene expression profiles of a T-cell line stimulated with native versus agonist peptides.

RESULTS

Numerous genes and gene clusters are identified as differentially expressed as a consequence of stimulation with the agonist peptide versus the native peptide; two genes, however, stand out in magnitude: the chemokine lymphotactin and granzyme B. In particular, lymphotactin expression is >12 times more pronounced in agonist-stimulated T cells. An ELISA assay was developed that confirmed marked lymphotactin secretion in T cells when stimulated with the agonist versus the native peptide. A chemotaxis assay also demonstrated the biological activity of the lymphotactin produced.

CONCLUSIONS

To our knowledge, these are the first studies of gene expression profiles of a defined T-cell line in response to stimulation with a defined antigen. They are also the first to compare, via cDNA microarray, responses of a T-cell line to (a) a tumor-associated self-antigen and (b) a native epitope versus an agonist epitope.

Authors+Show Affiliations

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12738714

Citation

Palena, Claudia, et al. "Differential Gene Expression Profiles in a Human T-cell Line Stimulated With a Tumor-associated Self-peptide Versus an Enhancer Agonist Peptide." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 9, no. 5, 2003, pp. 1616-27.
Palena C, Schlom J, Tsang KY. Differential gene expression profiles in a human T-cell line stimulated with a tumor-associated self-peptide versus an enhancer agonist peptide. Clin Cancer Res. 2003;9(5):1616-27.
Palena, C., Schlom, J., & Tsang, K. Y. (2003). Differential gene expression profiles in a human T-cell line stimulated with a tumor-associated self-peptide versus an enhancer agonist peptide. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 9(5), 1616-27.
Palena C, Schlom J, Tsang KY. Differential Gene Expression Profiles in a Human T-cell Line Stimulated With a Tumor-associated Self-peptide Versus an Enhancer Agonist Peptide. Clin Cancer Res. 2003;9(5):1616-27. PubMed PMID: 12738714.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential gene expression profiles in a human T-cell line stimulated with a tumor-associated self-peptide versus an enhancer agonist peptide. AU - Palena,Claudia, AU - Schlom,Jeffrey, AU - Tsang,Kwong-Yok, PY - 2003/5/10/pubmed PY - 2004/1/13/medline PY - 2003/5/10/entrez SP - 1616 EP - 27 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 9 IS - 5 N2 - PURPOSE: Previous studies have shown that a specific 9-mer amino acid epitope (designated CAP-1) of the human "self" tumor-associated carcinoembryonic antigen can be used to stimulate CD8+ T cells from peripheral blood mononuclear cells of carcinoma patients vaccinated with pox vector-based carcinoembryonic antigen vaccines. A T-cell receptor agonist epitope of CAP-1 (designated CAP1-6D) has been shown to enhance the stimulation of T cells over levels obtained using CAP-1. The purpose of this study was to analyze gene expression profiles in T cells stimulated with the native CAP-1 versus the agonist CAP1-6D peptide. EXPERIMENTAL DESIGN: Microarray analyses were conducted to analyze differential gene expression profiles of a T-cell line stimulated with native versus agonist peptides. RESULTS: Numerous genes and gene clusters are identified as differentially expressed as a consequence of stimulation with the agonist peptide versus the native peptide; two genes, however, stand out in magnitude: the chemokine lymphotactin and granzyme B. In particular, lymphotactin expression is >12 times more pronounced in agonist-stimulated T cells. An ELISA assay was developed that confirmed marked lymphotactin secretion in T cells when stimulated with the agonist versus the native peptide. A chemotaxis assay also demonstrated the biological activity of the lymphotactin produced. CONCLUSIONS: To our knowledge, these are the first studies of gene expression profiles of a defined T-cell line in response to stimulation with a defined antigen. They are also the first to compare, via cDNA microarray, responses of a T-cell line to (a) a tumor-associated self-antigen and (b) a native epitope versus an agonist epitope. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/12738714/Differential_gene_expression_profiles_in_a_human_T_cell_line_stimulated_with_a_tumor_associated_self_peptide_versus_an_enhancer_agonist_peptide_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12738714 DB - PRIME DP - Unbound Medicine ER -