[Improved expression of HLA-A* 2402-BSP in Escherichia coli and its tetramer preparation]

Sheng Wu Gong Cheng Xue Bao. 2007 Mar;23(2):284-91. doi: 10.1016/s1872-2075(07)60025-9.
[Article in Chinese]

Abstract

HLA-A* 2402 is one of the most frequently encountered HLA-A alleles in East Asian populations. In order to study the CD8+ T cell responses in Chinese populations, we have described the generation and functional test of HLA-A* 2402 tetramer loaded with HCMV pp65(341-349) peptide (QYDPVAALF, QYD). The cDNA of HLA-A* 2402 heavy chain was cloned by RT-PCR from one of the donors. DNA fragment encoding the ectodomain of HLA-A* 2402 heavy chain fused at its carboxyl-terminal a BirA substrate peptide (BSP) was amplified by PCR with the cloned heavy chain cDNA as a template. The wild-type gene of HLA-A* 2402-BSP was not expressed in Escherichia coli (E. coli), while mutant HLA-A* 2402-BSP gene with optimized codons was overexpressed as inclusion bodies in E. coli. Furthermore, the soluble HLA-A* 2402-QYD monomers were generated by in vitro refolding of washed inclusion bodies in the presence of beta2-microglobulin and QYD peptide. The tetramer was subsequently formed by mixing HLA-A* 2402-QYD monomers with streptavidin-PE at a molar ratio of 4:1. Flow cytometry analysis indicated that this tetramer possessed binding activity with specific CTL from HLA-A24+ donors and the frequencies of tetramer-binding CTL were 0.09% - 0.37% within total CD8+ T cells. This tetrameric agent provides a powerful tool to explore the secrets of CTL responses against HCMV antigens in HLA-A* 2402 individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carbon-Nitrogen Ligases / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / genetics
  • Escherichia coli Proteins / metabolism
  • Flow Cytometry
  • Gene Expression
  • HLA-A Antigens / chemistry*
  • HLA-A Antigens / genetics
  • HLA-A Antigens / metabolism*
  • HLA-A24 Antigen
  • Humans
  • Oligopeptides / genetics
  • Oligopeptides / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Multimerization
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Repressor Proteins / metabolism
  • Substrate Specificity
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism

Substances

  • Escherichia coli Proteins
  • HLA-A Antigens
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • Oligopeptides
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • Carbon-Nitrogen Ligases
  • birA protein, E coli