Monoclonal antibodies specific to human Δ42PD1: A novel immunoregulator potentially involved in HIV-1 and tumor pathogenesis

Lin Cheng, Xian Tang, Li Liu, Jie Peng, Kenji Nishiura, Allen Ka Loon Cheung, Jia Guo, Xilin Wu, Hang Ying Tang, Minghui An, Jingying Zhou, Ka Wai Cheung, Hui Wang, Xinyuan Guan, Zhiwei Wu*, Zhiwei Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

6 Citations (Scopus)

Abstract

We recently reported the identification of Δ42PD1, a novel alternatively spliced isoform of human PD1 that induces the production of pro-inflammatory cytokines from human peripheral blood mononuclear cells and enhances HIV-specific CD8+ T cell immunity in mice when engineered in a fusion DNA vaccine. The detailed functional study of Δ42PD1, however, has been hampered due to the lack of a specific monoclonal antibody (mAb). In this study, we generated 2 high-affinity mAbs, clones CH34 (IgG2b) and CH101 (IgG1), from Δ42PD1-immunized mice. They recognize distinct domains of Δ42PD1 as determined by a yeast surface-displaying assay and ELISA. Moreover, they recognize native Δ42PD1 specifically, but not PD1, on cell surfaces by both flow cytometry and immunohistochemical assays. Δ42PD1 appeared to be expressed constitutively on healthy human CD14+ monocytes, but its level of expression was down-regulated significantly during chronic HIV-1 infection. Since the level of Δ42PD1 expression on CD14+ monocytes was negatively correlated with the CD4 count of untreated patients in a cross-sectional study, Δ42PD1 may play a role in HIV-1 pathogenesis. Lastly, when examining Δ42PD1 expression in human esophageal squamous-cell carcinoma tissues, we found high-level expression of Δ42PD1 on a subset of tumor-infiltrating T cells. Our study, therefore, resulted in 2 Δ42PD1-specific mAbs that can be used to further investigate Δ42PD1, a novel immune regulatory protein implicated in HIV-1 and tumor pathogenesis as well as other immune diseases.

Original languageEnglish
Pages (from-to)620-629
Number of pages10
JournalmAbs
Volume7
Issue number3
DOIs
Publication statusPublished - 4 May 2015

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

User-Defined Keywords

  • Δ42PD1
  • ESCC
  • HIV-1
  • Monoclonal antibody
  • PD1
  • Tumor

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