Cross-presentation of HLA class I epitopes from exogenous NY-ESO-1 polypeptides by nonprofessional APCs Journal Article
| Authors: | Gnjatic, S.; Atanackovic, D.; Matsuo, M.; Jäger, E.; Lee, S. Y.; Valmori, D.; Chen, Y. T.; Ritter, G.; Knuth, A.; Old, L. J. |
| Article Title: | Cross-presentation of HLA class I epitopes from exogenous NY-ESO-1 polypeptides by nonprofessional APCs |
| Abstract: | NY-ESO-1, a germ cell Ag often detected in tumor tissues, frequently elicits Ab and CD8+ T cell responses in cancer patients. Overlapping long peptides spanning the NY-ESO-1 sequence have been used to map HLA class I-restricted epitopes recognized by NY-ESO-1-specific CD8+ T lymphocytes. To address the antigenicity of long peptides, we analyzed two synthetic 30-mer peptides from NY-ESO-1, polypeptides 80-109 and 145-174, for their capacity to be processed by APCs and to stimulate CD8+ T cells. By incubating APCs with polypeptides at different temperatures or in the presence of protease inhibitors, we found that NY-ESO-1 polypeptides were rapidly internalized by B cells, T2 cells, or PBLs and submitted to cellular proteolytic action to yield nonamer epitopes presented by HLA class I. Polypeptides were also immunogenic in vitro and stimulated the expansion of CD8+ T cells against naturally processed NY-ESO-1 epitopes in the context of three different HLA class I alleles. Polypeptides can thus serve as exogenous Ags that are cross-presented on HLA class I without requiring the action of professional APCs. These findings support innovative vaccination strategies using NY-ESO-1 polypeptides that would circumvent current limitations of HLA class I peptide vaccination, i.e., HLA eligibility criteria and knowledge of epitope, while allowing for facilitated immunogenicity in the presence of helper epitopes. |
| Keywords: | unclassified drug; human cell; cancer patient; t lymphocyte; cd8-positive t-lymphocytes; proteins; allele; cells, cultured; protein degradation; membrane proteins; in vitro study; b lymphocyte; antigen presentation; protein processing; amino acid sequence; molecular sequence data; antigens, neoplasm; immunogenicity; peptide fragments; vaccination; epitope; hla antigen class 1; histocompatibility antigens class i; temperature; epitopes, t-lymphocyte; proteinase inhibitor; antigen presenting cell; antigen-presenting cells; hla antigens; polypeptide; antigenicity; protein ny eso 1; humans; human; priority journal; article |
| Journal Title: | Journal of Immunology |
| Volume: | 170 |
| Issue: | 3 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2003-02-01 |
| Start Page: | 1191 |
| End Page: | 1196 |
| Language: | English |
| PUBMED: | 12538675 |
| PROVIDER: | scopus |
| DOI: | 10.4049/jimmunol.170.3.1191 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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