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

TitleMonoclonal antibodies specific to human Δ42PD1: A novel immunoregulator potentially involved in HIV-1 and tumor pathogenesis
Authors
KeywordsD42PD1
ESCC
HIV-1
Monoclonal antibody
PD1
Tumor
Issue Date2015
PublisherLandes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/mabs/
Citation
MAbs, 2015, v. 7 n. 3, p. 620-629 How to Cite?
AbstractWe 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 HIVspecific 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 CΔ4 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. © 2015, Taylor and Francis Group, LLC.
Persistent Identifierhttp://hdl.handle.net/10722/216805
ISSN
2023 Impact Factor: 5.6
2023 SCImago Journal Rankings: 1.702
ISI Accession Number ID
Grants

 

DC FieldValueLanguage
dc.contributor.authorCheng, L-
dc.contributor.authorTang, X-
dc.contributor.authorLiu, L-
dc.contributor.authorPENG, J-
dc.contributor.authorNishiura, K-
dc.contributor.authorCheung, KLA-
dc.contributor.authorGUO, J-
dc.contributor.authorWU, X-
dc.contributor.authorTang, H-
dc.contributor.authorAn, M-
dc.contributor.authorZHOU, J-
dc.contributor.authorCheung, KW-
dc.contributor.authorWang, H-
dc.contributor.authorGuan, X-
dc.contributor.authorWu, Z-
dc.contributor.authorChen, Z-
dc.date.accessioned2015-09-18T05:39:10Z-
dc.date.available2015-09-18T05:39:10Z-
dc.date.issued2015-
dc.identifier.citationMAbs, 2015, v. 7 n. 3, p. 620-629-
dc.identifier.issn1942-0862-
dc.identifier.urihttp://hdl.handle.net/10722/216805-
dc.description.abstractWe 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 HIVspecific 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 CΔ4 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. © 2015, Taylor and Francis Group, LLC.-
dc.languageeng-
dc.publisherLandes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/mabs/-
dc.relation.ispartofMAbs-
dc.rightsPREPRINT This is a preprint of an article whose final and definitive form has been published in the [JOURNAL TITLE] [year of publication] [copyright Taylor & Francis]; [JOURNAL TITLE] is available online at: http://www.informaworld.com/smpp/ with the open URL of your article POSTPRINT This is an Accepted Manuscript of an article published by Taylor & Francis in [JOURNAL TITLE] on [date of publication], available online: http://wwww.tandfonline.com/[Article DOI]-
dc.subjectD42PD1-
dc.subjectESCC-
dc.subjectHIV-1-
dc.subjectMonoclonal antibody-
dc.subjectPD1-
dc.subjectTumor-
dc.titleMonoclonal antibodies specific to human Δ42PD1: A novel immunoregulator potentially involved in HIV-1 and tumor pathogenesis-
dc.typeArticle-
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hk-
dc.identifier.emailCheung, KLA: allenc@hku.hk-
dc.identifier.emailCheung, KW: fayekw@hku.hk-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityLiu, L=rp00268-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.doi10.1080/19420862.2015.1016695-
dc.identifier.pmid25692916-
dc.identifier.scopuseid_2-s2.0-84945184392-
dc.identifier.hkuros254435-
dc.identifier.volume7-
dc.identifier.issue3-
dc.identifier.spage620-
dc.identifier.epage629-
dc.identifier.isiWOS:000353957600015-
dc.publisher.placeUnited States-
dc.relation.projectInvestigation of effects and molecular mechanisms of FGFR2-positive cancer-associate fibroblasts on tumor microenvironment in esophageal squamous cell carcinoma-
dc.identifier.issnl1942-0862-

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