Vaccination with recombinant NY-ESO-1 protein elicits immunodominant HLA-DR52b-restricted CD4+ T cell responses with a conserved T cell receptor repertoire Journal Article
| Authors: | Bioley, G.; Dousset, C.; Yeh, A.; Dupont, B.; Bhardwaj, N.; Mears, G.; Old, L. J.; Ayyoub, M.; Valmori, D. |
| Article Title: | Vaccination with recombinant NY-ESO-1 protein elicits immunodominant HLA-DR52b-restricted CD4+ T cell responses with a conserved T cell receptor repertoire |
| Abstract: | Purpose: ESO is a tumor-specific antigen with wide expression in human tumors of different histologic types and remarkable spontaneous immunogenicity.We have previously shown that specificTH1and antibody responses can be elicited in patients with no detectable preexisting immune responses by vaccination with rESO administered with Montanide ISA-51and CpG ODN 7909.The purpose of the present study was to characterize vaccine-induced ESO-specific CD4+ Tcell responses. Experimental Design:We generated CD4+ T cell clones from patient C2, who had the highest CD4+ Tcell response to the vaccine, and analyzed their fine specificity and HLA class II restriction to determine the recognized epitope.We then assessed the response to the identified epitope in all vaccinated patients expressing the corresponding HLA class II allele. Results: We found that ESO-specific CD4+ T cell clones from patient C2 recognize peptide ESO119-143 (core region 123-137) presented by HLA-DR52b (HLA-DRB3*0202), a MHC class II allele expressed by about half of Caucasians. Importantly, following vaccination, all patients expressing DR52b developed significant responses to the identified epitope, accounting for, on average, half of the total CD4+ T cell responses to the 119-143 immunodominant region. In addition, analysis of ESO-specific DR52b-restricted CD4+ Tcells at the clonal level revealed significant conservation ofT cell receptor usage among different individuals. Conclusions: The identification of a DR52b-restricted epitope from ESO that is immunodominant in the context of vaccine-elicited immune responses is instrumental for the immunologic monitoring of vaccination trials targeting this important tumor antigen. © 2009 American Association for Cancer Research. |
| Keywords: | clinical article; controlled study; unclassified drug; human cell; antigen expression; allele; cells, cultured; membrane proteins; t lymphocyte receptor; antigen presentation; lymphocyte activation; immune response; amino acid sequence; antigens, neoplasm; cancer vaccines; antigen specificity; receptors, antigen, t-cell; ny eso 1 antigen; immunogenicity; cpg oligodeoxynucleotide; cpg oligodeoxynucleotide 7909; hla antigen class 2; hla dr antigen; hla dr52b antigen; major histocompatibility antigen class 2; montanide isa 51; recombinant antigen; antibody response; antigen recognition; cancer immunization; cd4+ t lymphocyte; lymphocyte clone; cd4-positive t-lymphocytes; epitope mapping; hla-dr antigens; immunodominant epitopes; peptide fragments; recombinant proteins; substrate specificity; t-cell antigen receptor specificity; vaccination |
| Journal Title: | Clinical Cancer Research |
| Volume: | 15 |
| Issue: | 13 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2009-07-01 |
| Start Page: | 4467 |
| End Page: | 4474 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-09-0582 |
| PUBMED: | 19531622 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "CODEN: CCREF" - "Source: Scopus" |
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