MAGE-A3161-175 contains an HLA-DRβ4 restricted natural epitope poorly formed through indirect presentation by dendritic cells

Jill Marturano, Renato Longhi, Giulia Casorati, Maria Pia Protti

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We report here that HLA-DRβ4*01 restricted MAGE-A3 161-175 specific CD4+ T cells from a healthy donor recognize a naturally processed epitope formed through the exogenous but not the endogenous pathway. However, the intensity of recognition of the native epitope by MAGE-A3161-175 specific CD4+ T cells strongly depends on the antigen presenting cells and the amount of protein available for processing. EBV-transformed lymphoblastoid cells (LCLs) and melanoma cells engineered to express MAGE-A3 in the endosomal/lysosomal compartment were strongly recognized while autologous dendritic cells loaded with lysate from MAGE-A3 expressing cells were, although significantly, poorly recognized. To prove that the amount of antigen available for processing was a key factor determining the different response LCLs were sorted by MAGE-A3 expression. The response intensity correlated with the amount of MAGE-A3 expressed by the cells. Collectively, these results suggest that different antigen presenting cells with different amount of antigen available for processing as well as protease activity are important factors in determining the epitope repertoire produced in vivo, and therefore reliable tools should be used when testing recognition of native epitopes by peptide specific CD4+ T cells.

Original languageEnglish
Pages (from-to)207-215
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume57
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

HLA-DR4 Antigen
Dendritic Cells
Epitopes
Antigen Presentation
Antigen-Presenting Cells
T-Lymphocytes
Human Herpesvirus 4
Melanoma
Peptide Hydrolases
Peptides
Proteins

Keywords

  • Antigen processing
  • CD4 T cells
  • MAGE-A3
  • MHC class II epitopes
  • Native epitopes

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

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abstract = "We report here that HLA-DRβ4*01 restricted MAGE-A3 161-175 specific CD4+ T cells from a healthy donor recognize a naturally processed epitope formed through the exogenous but not the endogenous pathway. However, the intensity of recognition of the native epitope by MAGE-A3161-175 specific CD4+ T cells strongly depends on the antigen presenting cells and the amount of protein available for processing. EBV-transformed lymphoblastoid cells (LCLs) and melanoma cells engineered to express MAGE-A3 in the endosomal/lysosomal compartment were strongly recognized while autologous dendritic cells loaded with lysate from MAGE-A3 expressing cells were, although significantly, poorly recognized. To prove that the amount of antigen available for processing was a key factor determining the different response LCLs were sorted by MAGE-A3 expression. The response intensity correlated with the amount of MAGE-A3 expressed by the cells. Collectively, these results suggest that different antigen presenting cells with different amount of antigen available for processing as well as protease activity are important factors in determining the epitope repertoire produced in vivo, and therefore reliable tools should be used when testing recognition of native epitopes by peptide specific CD4+ T cells.",
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AU - Longhi, Renato

AU - Casorati, Giulia

AU - Protti, Maria Pia

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AB - We report here that HLA-DRβ4*01 restricted MAGE-A3 161-175 specific CD4+ T cells from a healthy donor recognize a naturally processed epitope formed through the exogenous but not the endogenous pathway. However, the intensity of recognition of the native epitope by MAGE-A3161-175 specific CD4+ T cells strongly depends on the antigen presenting cells and the amount of protein available for processing. EBV-transformed lymphoblastoid cells (LCLs) and melanoma cells engineered to express MAGE-A3 in the endosomal/lysosomal compartment were strongly recognized while autologous dendritic cells loaded with lysate from MAGE-A3 expressing cells were, although significantly, poorly recognized. To prove that the amount of antigen available for processing was a key factor determining the different response LCLs were sorted by MAGE-A3 expression. The response intensity correlated with the amount of MAGE-A3 expressed by the cells. Collectively, these results suggest that different antigen presenting cells with different amount of antigen available for processing as well as protease activity are important factors in determining the epitope repertoire produced in vivo, and therefore reliable tools should be used when testing recognition of native epitopes by peptide specific CD4+ T cells.

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