Assessment of vaccine-induced CD4 T cell responses to the 119-143 immunodominant region of the tumor-specific antigen NY-ESO-1 using DRB1*0101 tetramers.

Abstract

PURPOSE:

NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is presently viewed as an important model antigen for the development of generic anticancer vaccines. The ESO(119-143) region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we generated DRB1*0101/ESO(119-143) tetramers and used them to assess CD4 T-cell responses in vaccinated patients expressing DRB1*0101 (DR1).

EXPERIMENTAL DESIGN:

We generated tetramers of DRB1*0101 incorporating peptide ESO(119-143) using a previously described strategy. We assessed ESO(119-143)-specific CD4 T cells in peptide-stimulated postvaccine cultures using the tetramers. We isolated DR1/ESO(119-143) tetramer(+) cells by cell sorting and characterized them functionally. We assessed vaccine-induced CD4(+) DR1/ESO(119-143) tetramer(+) T cells ex vivo and characterized them phenotypically.

RESULTS:

Staining of cultures from vaccinated patients with DR1/ESO(119-143) tetramers identified vaccine-induced CD4 T cells. Tetramer(+) cells isolated by cell sorting were of T(H)1 type and efficiently recognized full-length ESO. We identified ESO(123-137) as the minimal optimal epitope recognized by DR1-restricted ESO-specific CD4 T cells. By assessing DR1/ESO(119-143) tetramer(+) cells using T cell receptor (TCR) β chain variable region (Vβ)-specific antibodies, we identified several frequently used Vβ. Finally, direct ex vivo staining of patients' CD4 T cells with tetramers allowed the direct quantification and phenotyping of vaccine-induced ESO-specific CD4 T cells.

CONCLUSIONS:

The development of DR1/ESO(119-143) tetramers, allowing the direct visualization, isolation, and characterization of ESO-specific CD4 T cells, will be instrumental for the evaluation of spontaneous and vaccine-induced immune responses to this important tumor antigen in DR1-expressing patients.

• Authors: Maha Ayyoub, Pascale Pignon, Danijel Dojcinovic, Isabelle Raimbaud, Lloyd J Old, Immanuel Luescher, Danila Valmori
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 18 Pg. 4607-15 (Sep 15 2010) ISSN: 1557-3265 [Electronic] United States
• PMID: 20670945 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2010 AACR.

Chemical References

• Antigens, Neoplasm
• CTAG1B protein, human
• Cancer Vaccines
• HLA-A Antigens
• HLA-DRB1 Chains
• HLA-DRB1*01:01 antigen
• Immunodominant Epitopes
• Membrane Proteins
• Neoplasm Proteins
• Recombinant Fusion Proteins
• Vaccines, Synthetic

Topics

• Amino Acid Sequence
• Animals
• Antigen-Antibody Reactions (immunology)
• Antigens, Neoplasm (chemistry, immunology, metabolism, pharmacology)
• CD4-Positive T-Lymphocytes (cytology, drug effects, immunology)
• Cancer Vaccines (chemical synthesis, chemistry, pharmacology)
• Cells, Cultured
• Clinical Trials as Topic
• HLA-A Antigens (chemistry, immunology, metabolism, pharmacology)
• HLA-DRB1 Chains
• Humans
• Immunity, Cellular (drug effects, immunology)
• Immunodominant Epitopes (immunology)
• Membrane Proteins (chemistry, immunology, metabolism, pharmacology)
• Mice
• Neoplasm Proteins (chemistry, immunology)
• Protein Multimerization (physiology)
• Recombinant Fusion Proteins (chemical synthesis, immunology, metabolism, pharmacology)
• Vaccination (methods)
• Vaccines, Synthetic (chemistry, immunology, metabolism)
• Validation Studies as Topic