Identification of a human cyclin D1-derived peptide that induces human cytotoxic CD4 T cells Journal Article
| Authors: | Dao, T.; Korontsvit, T.; Zakhaleva, V.; Haro, K.; Packin, J.; Scheinberg, D. A. |
| Article Title: | Identification of a human cyclin D1-derived peptide that induces human cytotoxic CD4 T cells |
| Abstract: | Cyclin D1 is over-expressed in various human tumors and therefore can be a potential oncogenic target antigen. However, only a limited number of T cell epitopes has been characterized. We aimed at identifying human cyclin D1-derived peptides that include both CD4 and CD8 T cell epitopes and to test if such multi-epitope peptides could yield improved cytotoxic CD8 T cell responses as well as cytotoxic CD4 T cells. Five HLA-DR.B1-binding peptides containing multiple overlapping CD4 epitopes and HLA-A0201-restricted CD8 T cell epitopes were predicted by computer algorithms. Immunogenicity of the synthetic peptides was assessed by stimulating T cells from healthy donors in vitro and the epitope recognition was measured by IFN-γ ELISPOT and <sup>51</sup>Chromium release assays. A HLA-DR.B1 peptide, designed "DR-1", in which a HLA-A0201-binding epitopes (D1-1) was imbedded, induced CD3 T cell responses against both DR-1 and D1-1 peptides in IFN-γ ELISPOT assay. This suggested processing of the shorter D1-1 epitope from the DR-1 sequence. However, only DR-1-stimulated CD4 or CD3 T cells possessed cytotoxicity against peptide-pulsed autologous DCs and a cancer cell line, that expresses a high level of cyclin D1. Monoclonal antibody to HLA-DR abrogated the epitope-specific responses of both CD3 and CD4 T cells, demonstrating class II-mediated killing. Our studies suggest a possible role of CD4 T cells in anti-tumor immunity as cytotoxic effectors against HLA-DR expressing cancers and provide a rationale for designing peptide vaccines that include CD4 epitopes. © 2009 Dao et al. |
| Keywords: | controlled study; unclassified drug; gene sequence; human cell; flow cytometry; molecular genetics; cd8+ t lymphocyte; phenotype; cytology; metabolism; interleukin 2; gene expression; drug effect; peptide; cell line, tumor; enzyme linked immunosorbent assay; gene number; immunology; chemistry; immune response; amino acid sequence; molecular sequence data; gamma interferon; gene identification; hla antigen class 2; hla dr antigen; cd4+ t lymphocyte; cd4-positive t-lymphocytes; epitope; cytotoxic t lymphocyte; tumor cell line; t-lymphocytes, cytotoxic; hla antigen class 1; histocompatibility antigens class i; peptides; tumor immunity; cytokine production; upregulation; enzyme-linked immunosorbent assay; t cell depletion; cyclin d1; hla a0201 antigen; hla dr b1 antigen; antigen binding; cd3+ t lymphocyte; cell stimulation; cytokine release; enzyme linked immunospot assay; histocompatibility antigens class ii |
| Journal Title: | PLoS ONE |
| Volume: | 4 |
| Issue: | 8 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2009-08-25 |
| Start Page: | e6730 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0006730 |
| PUBMED: | 19707583 |
| PROVIDER: | scopus |
| PMCID: | PMC2726944 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "Art. No.: e6730" - "Source: Scopus" |
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29Zakhaleva -
53Korontsvit -
5
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2
Packin
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