Refinement in the production and purification of recombinant HCMV IE1-pp65 protein for the generation of epitope-specific T cell immunity

Protein Expr Purif. 2008 Sep;61(1):22-30. doi: 10.1016/j.pep.2008.05.001. Epub 2008 May 14.

Abstract

Human cytomegalovirus (HCMV) remains one of the most common opportunistic infections causing disease following stem cell transplantation, despite the availability of anti-viral therapies. Adoptive immunotherapy has the potential to further aid in counteracting chronic viral reactivation and subsequent disease by restoring viral immunity through the transfer of virus-specific T cells from transplant donors to their recipients. Our study refines the production and purification of a recombinant HCMV protein containing two of the most immunodominant antigens (IE1 and pp65) for the generation of polyclonal HCMV-specific T cells. In doing so, a 6x His-tagged IE1-pp65 protein was generated using a serum-free baculovirus/insect cell expression system and soluble IE1-pp65 protein was subsequently purified using Ni-NTA affinity chromatography under stringent conditions to obtain a highly pure product. The ability of the recombinant IE1-pp65 protein to elicit a functional T cell mediated immune response was demonstrated by the vigorous reactivation and expansion of HLA-A2-restricted pp65(495-503)-specific CD8+ T cells. This recombinant IE1-pp65 protein can potentially generate a multitude of HLA-restricted HCMV-specific T cells, providing a better alternative to using costly overlapping peptides or HCMV lysates for expansion of T cells for use in adoptive immunotherapy strategies.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Baculoviridae / genetics
  • Base Sequence
  • CD8-Positive T-Lymphocytes / immunology*
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Immediate-Early Proteins / chemistry
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / immunology
  • Immediate-Early Proteins / isolation & purification*
  • Immunodominant Epitopes / immunology*
  • Molecular Sequence Data
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics*
  • Phosphoproteins / immunology
  • Phosphoproteins / isolation & purification*
  • Polymerase Chain Reaction
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification
  • Spodoptera
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics*
  • Viral Matrix Proteins / immunology
  • Viral Matrix Proteins / isolation & purification*

Substances

  • DNA Primers
  • IE1-pp65 recombinant protein, Human cytomegalovirus
  • Immediate-Early Proteins
  • Immunodominant Epitopes
  • Phosphoproteins
  • Recombinant Proteins
  • Viral Matrix Proteins