Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4*0101-0103 and recognized by CD4+ T lymphocytes of patients with NY-ESO-1-expressing melanoma Journal Article
| Authors: | Jäger, E.; Jäger, D.; Karbach, J.; Chen, Y. T.; Ritter, G.; Nagata, Y.; Gnjatic, S.; Stockert, E.; Arand, M.; Old, L. J.; Knuth, A. |
| Article Title: | Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4*0101-0103 and recognized by CD4+ T lymphocytes of patients with NY-ESO-1-expressing melanoma |
| Abstract: | NY-ESO-1 is a member of the cancer-testis family of tumor antigens that elicits strong humoral and cellular immune responses in patients with NY-ESO-1-expressing cancers. Since CD4+ T lymphocytes play a critical role in generating antigen-specific cytotoxic T lymphocyte and anti-body responses, we searched for NY-ESO-1 epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules. Autologous monocyte-derived dendritic cells of cancer patients were incubated with recombinant NY-ESO-1 protein and used in enzyme-linked immunospot (ELISPOT) assays to detect NY-ESO-1-specific CD4+ T lymphocyte responses. To identify possible epitopes presented by distinct HLA class II alleles, overlapping 18-mer peptides derived from NY-ESO-1 were synthetized and tested for recognition by CD4+ T lymphocytes in autologous settings. We identified three NY-ESO-1-derived peptides presented by DRB4(*)0101-0103 and recognized by CD4+ T lymphocytes of two melanoma patients sharing these HLA class II alleles. Specificity of recognition was confirmed by proliferation assays. The characterization of HLA class II-restricted epitopes will be useful for the assessment of spontaneous and vaccine-induced immune responses of cancer patients against defined tumor antigens. Further, the therapeutic efficacy of active immunization using antigenic HLA class I-restricted peptides may be improved by adding HLA class II-presented epitopes. |
| Keywords: | clinical article; human cell; antigen expression; t lymphocyte; proteins; melanoma; cell line; membrane proteins; alleles; tumor antigen; dendritic cells; cellular immunity; immune response; amino acid sequence; molecular sequence data; antigens, neoplasm; hla antigen class 2; hla dr antigen; antibody response; cd4-positive t-lymphocytes; hla-dr antigens; recombinant proteins; epitope; humoral immunity; antigen-presenting cells; active immunization; humans; human; priority journal; article; hla class ii-restricted ny-eso-1 epitopes · cd4+ t cell recognition |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 191 |
| Issue: | 4 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2000-02-21 |
| Start Page: | 625 |
| End Page: | 630 |
| Language: | English |
| DOI: | 10.1084/jem.191.4.625 |
| PUBMED: | 10684854 |
| PROVIDER: | scopus |
| PMCID: | PMC2195843 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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