Retrovirally transduced human dendritic cells can generate T cells recognizing multiple MHC class I and class II epitopes from the melanoma antigen glycoprotein 100

J Immunol. 2001 Oct 15;167(8):4758-64. doi: 10.4049/jimmunol.167.8.4758.

Abstract

Involvement of tumor-Ag specific CD4(+) and CD8(+) T cells could be critical in the generation of an effective immunotherapy for cancer. In an attempt to optimize the T cell response against defined tumor Ags, we previously developed a method allowing transgene expression in human dendritic cells (DCs) using retroviral vectors. One advantage of using gene-modified DCs is the potential ability to generate CD8(+) T cells against multiple class I-restricted epitopes within the Ag, thereby eliciting a broad antitumor immune response. To test this, we generated tumor-reactive CD8(+) T cells with DCs transduced with the melanoma Ag gp100, for which a number of HLA-A2-restricted epitopes have been described. Using gp100-transduced DCs, we were indeed able to raise T cells recognizing three distinct HLA-A2 epitopes within the Ag, gp100(154-162), gp100(209-217), and gp100(280-288). We next tested the ability of transduced DCs to raise class II-restricted CD4(+) T cells. Interestingly, stimulation with gp100-transduced DCs resulted in the generation of CD4(+) T cells specific for a novel HLA-DRbeta1*0701-restricted epitope of gp100. The minimal determinant of this epitope was defined as gp100(174-190) (TGRAMLGTHTMEVTVYH). These observations suggest that retrovirally transduced DCs have the capacity to present multiple MHC class I- and class II-restricted peptides derived from a tumor Ag, thereby eliciting a robust immune response against that Ag.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation
  • Antigens, CD34 / isolation & purification
  • Dendritic Cells / immunology*
  • Epitopes
  • Genetic Vectors
  • HLA-A2 Antigen / immunology
  • HLA-DR Antigens / immunology
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Melanoma / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / immunology
  • Peptides
  • Retroviridae / genetics
  • T-Lymphocytes / immunology*
  • Transformation, Genetic
  • gp100 Melanoma Antigen

Substances

  • Antigens, CD34
  • Epitopes
  • HLA-A2 Antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Peptide Fragments
  • Peptides
  • gp100 Melanoma Antigen
  • gp100(280-288) melanoma antigen peptide