CD8+ T cell responses against a dominant cryptic HLA-A2 epitope after NY-ESO-1 peptide immunization of cancer patients Journal Article
| Authors: | Gnjatic, S.; Jäger, E.; Chen, W.; Altorki, N. K.; Matsuo, M.; Lee, S. Y.; Chen, Q.; Nagata, Y.; Atanackovic, D.; Chen, Y. T.; Ritter, G.; Cebon, J.; Knuth, A.; Old, L. J. |
| Article Title: | CD8+ T cell responses against a dominant cryptic HLA-A2 epitope after NY-ESO-1 peptide immunization of cancer patients |
| Abstract: | NY-ESO-1 is a germ cell antigen aberrantly expressed in different tumor types that elicits strong humoral and cellular immune responses in cancer patients, Monitoring spontaneous CD8+ T cell responses against NY-ESO-1 peptides 157-165 (59C) and 157-167 (S11L) in a series of HLA-A2+ cancer patients showed that these two peptides had overlapping antigenic profiles and were equally immunogenic. However, discrepancies between S9C and S11L reactivities were observed upon vaccination with both peptides to generate or boost T cell responses to NY-ESO-1 in cancer patients. We here analyze the fine specificity of these responses and describe an HLA-A2-restricted epitope, NY-ESO-1 peptide 159-167 (L9L), which is strongly recognized by CD8+ T cells as a result of peptide vaccination of cancer patients. Responses to L9L were stimulated by 511L and appeared early in the course of vaccination, independently of S9C responses. However, L9L-specific CD8+ T cells failed to recognize tumor cells naturally expressing NY-ESO-1 or B lymphoblastoid cells transduced with NY-ESO-1. Processing of L9L could be rescued after IFN-γ treatment of tumor cells or by dendritic cells pulsed with NY-ESO-1 protein/antibody immune complexes. The present results demonstrate a dual specificity within peptide 511L, with 59C as the natural antigenic tumor epitope, and L9L as a cryptic epitope with dominant immunogenicity upon vaccination that diverts the immune response from tumor recognition. These unanticipated findings raise questions about the use of 511L in the clinic and emphasize the importance of analyzing the fine specificity of vaccine-induced T cell responses in patients as a basis for constructing effective cancer vaccines. |
| Keywords: | clinical article; controlled study; unclassified drug; human cell; nonhuman; cancer patient; neoplasms; cd8 antigen; t lymphocyte; cd8-positive t-lymphocytes; proteins; dendritic cell; membrane proteins; peptide; cellular immunity; antigens, neoplasm; gamma interferon; cancer vaccine; cancer vaccines; antigen specificity; immunogenicity; antigen recognition; cancer immunization; immunodominant epitopes; epitope; tumor cell; target cell; granulocyte colony stimulating factor; major histocompatibility complex restriction; hla a2 antigen; hla-a2 antigen; antigen antibody complex; cross reactions; lymphoblastoid cell; antigen ny eso 1; cancer; humans; human; priority journal; article; peptide s11l; peptide s9c |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 99 |
| Issue: | 18 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2002-09-03 |
| Start Page: | 11813 |
| End Page: | 11818 |
| Language: | English |
| DOI: | 10.1073/pnas.142417699 |
| PUBMED: | 12186971 |
| PROVIDER: | scopus |
| PMCID: | PMC129351 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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