Dissecting cytotoxic T cell responses towards the NY-ESO-1 protein by peptide/MHC-specific antibody fragments Journal Article
| Authors: | Held, G.; Matsuo, M.; Epel, M.; Gnjatic, S.; Ritter, G.; Lee, S. Y.; Tai, T. Y.; Cohen, C. J.; Old, L. J.; Pfreundschuh, M.; Reiter, Y.; Hoogenboom, H. R.; Renner, C. |
| Article Title: | Dissecting cytotoxic T cell responses towards the NY-ESO-1 protein by peptide/MHC-specific antibody fragments |
| Abstract: | NY-ESO-1 is a germ cell antigen aberrantly expressed by different tumor types that elicits strong humoral and cellular immune responses, representing one of the most promising candidates for vaccination of cancer patients. A detailed analysis of CD8 + T cells generated in vaccine trials using NY-ESO-1 derived peptides (157-165 and 157-167) revealed that the dominant immune response was directed against a cryptic epitope (159-167) diverting the immune response from tumor recognition. Only CTL reactivity to the NY-ESO-1 157-165 peptide appeared to be capable of lysing NY-ESO-1/HLA-A0201-expressing tumor cells. To study the process of NY-ESO-1 peptide presentation by tumor cells in more detail we generated a high-affinity (K D=60 nM) antibody fragment that specifically recognizes the NY-ESO-1 157-165 peptide/HLA-A0201 complex. Peptide variants such as the NY-ESO-1 157-167 peptide or the cryptic NY-ESO-1 159-167 peptide were not recognized. The antibody fragment blocked in a dose-dependent fashion the recognition of NY-ESO-1/HLA-A2-positive tumor cells by NY-ESO-1 157-165 peptide-specific CD8 + T cells. This antibody fragment is a novel reagent that binds with TCR-like specificity to the NY-ESO-1 157-165/HLA-A2 complex thus distinguishing between CTL responses against immunological meaningful or cryptic NY-ESO-1-derived peptides. It may therefore become a useful monitoring tool for the development of NY-ESO-1-based cancer vaccines. © 2004 Wiley-VCH Verlag GmbH & Co. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; flow cytometry; protein conformation; cd8 antigen; t lymphocyte; germ cell; membrane proteins; cell line, tumor; transfection; antigen presentation; cellular immunity; amino acid sequence; antigens, neoplasm; cancer vaccines; immunodominant epitopes; ctl; epitope; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; tumor cell; peptides; antibody specificity; enzyme-linked immunosorbent assay; major histocompatibility complex; humoral immunity; protein variant; hla antigen; antibody affinity; hla a2 antigen; immunoglobulin f(ab) fragment; major histocompatibility antigen; immunoglobulin fab fragments; protein ny eso 1; humans; human; priority journal; article; peptide processing; peptide/mhc complexes; phage library; cell antigen |
| Journal Title: | European Journal of Immunology |
| Volume: | 34 |
| Issue: | 10 |
| ISSN: | 0014-2980 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 2004-10-01 |
| Start Page: | 2919 |
| End Page: | 2929 |
| Language: | English |
| DOI: | 10.1002/eji.200425297 |
| PROVIDER: | scopus |
| PUBMED: | 15368308 |
| DOI/URL: | |
| Notes: | Eur. J. Immunol. -- Cited By (since 1996):44 -- Export Date: 16 June 2014 -- CODEN: EJIMA -- Source: Scopus |
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