Dissecting cytotoxic T cell responses towards the NY-ESO-1 protein by peptide/MHC-specific antibody fragments

Eur J Immunol. 2004 Oct;34(10):2919-29. doi: 10.1002/eji.200425297.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibody Specificity / immunology*
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunoglobulin Fab Fragments / immunology*
  • Major Histocompatibility Complex / immunology*
  • Membrane Proteins / immunology*
  • Peptides / immunology*
  • Protein Conformation
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection


  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • Immunodominant Epitopes
  • Immunoglobulin Fab Fragments
  • Membrane Proteins
  • Peptides