Antibodies and Lentiviruses That Specifically Recognize a T Cell Epitope Derived from HIV-1 Nef Protein and Presented by HLA-C

Herschhorn, Alon; Marasco, Wayne A.; Hizi, Amnon

doi:10.4049/jimmunol.1001561

Cited by 23 publications

(23 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 48 h, approximately half a million cells were analyzed by flow cytometry as previously described 55 , but with primary antibody incubation for 30 min, and secondary antibody (Allophycocyaninconjugated F(ab’)2 fragment donkey anti-human IgG antibody, Jackson ImmunoResearch Laboratories) incubation for 15 min, both at room temperature. Cells were analyzed with a BD FACSCanto II flow cytometer (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

Mao

Wang

et al. 2012

Nat Struct Mol Biol

Self Cite

147

158

View full text Add to dashboard Cite

The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric gp160 precursor into three gp120 and three gp41 subunits. Here we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain, and a gp120 trimer association domain composed of the V1/V2 and V3 variable regions. The cage-like architecture, which is unique among characterized viral envelope proteins, restricts antibody access, reflecting requirements imposed by HIV-1 persistence in the host.

show abstract

Section: Methodsmentioning

confidence: 99%

Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

Mao

Wang

et al. 2012

Nat Struct Mol Biol

Self Cite

147

158

View full text Add to dashboard Cite

show abstract

“…Half a million cells were analyzed by flow cytometry as previously described [67], but with primary antibody incubation for 30 min, and secondary antibody (R-Phycoerythrin-conjugated goat anti-mouse IgG, Invitrogen) incubation for 10 min, both at room temperature. Cells were analyzed with a BD FACSCanto II flow cytometer (BD Biosciences) and results were displayed using Flow Jo software (Tree Star).…”

Section: Methodsmentioning

confidence: 99%

An Inducible Cell-Cell Fusion System with Integrated Ability to Measure the Efficiency and Specificity of HIV-1 Entry Inhibitors

et al. 2011

Self Cite

View full text Add to dashboard Cite

HIV-1 envelope glycoproteins (Envs) mediate virus entry by fusing the viral and target cell membranes, a multi-step process that represents an attractive target for inhibition. Entry inhibitors with broad-range activity against diverse isolates of HIV-1 may be extremely useful as lead compounds for the development of therapies or prophylactic microbicides. To facilitate the identification of such inhibitors, we have constructed a cell-cell fusion system capable of simultaneously monitoring inhibition efficiency and specificity. In this system, effector cells stably express a tetracycline-controlled transactivator (tTA) that enables tightly inducible expression of both HIV-1 Env and the Renilla luciferase (R-Luc) reporter protein. Target cells express the HIV-1 receptors, CD4 and CCR5, and carry the firefly luciferase (F-Luc) reporter gene under the control of a tTA-responsive promoter. Thus, Env-mediated fusion of these two cell types allows the tTA to diffuse to the target cell and activate the expression of the F-Luc protein. The efficiency with which an inhibitor blocks cell-cell fusion is measured by a decrease in the F-Luc activity, while the specificity of the inhibitor is evaluated by its effect on the R-Luc activity. The system exhibited a high dynamic range and high Z'-factor values. The assay was validated with a reference panel of inhibitors that target different steps in HIV-1 entry, yielding inhibitory concentrations comparable to published virus inhibition data. Our system is suitable for large-scale screening of chemical libraries and can also be used for detailed characterization of inhibitory and cytotoxic properties of known entry inhibitors.

show abstract

“…45). Their rationale was to target HIV-1-infected cells that express Fas receptor and to mediate the specific killing of HIV-1-infected cells by Fas-FasR-induced apoptosis.…”

Section: Targeting Virus-infected Cellsmentioning

confidence: 99%

T-cell-receptor-like antibodies – generation, function and applications

Dahan

Reiter

2012

Expert Rev. Mol. Med.

View full text Add to dashboard Cite

Tumour and virus-infected cells are recognised by CD8+ cytotoxic T cells that, in response, are activated to eliminate these cells. In order to be activated, the clonotypic T-cell receptor (TCR) needs to encounter a specific peptide antigen presented by the membrane surface major histocompatibility complex (MHC) molecule. Cells that have undergone malignant transformation or viral infection present peptides derived from tumour-associated antigens or viral proteins on their MHC class I molecules. Therefore, disease-specific MHC-peptide complexes are desirable targets for immunotherapeutic approaches. One such approach transforms the unique fine specificity but low intrinsic affinity of TCRs to MHC-peptide complexes into high-affinity soluble antibody molecules endowed with a TCR-like specificity towards tumour or viral epitopes. These antibodies, termed TCR-like antibodies, are being developed as a new class of immunotherapeutics that can target tumour and virus-infected cells and mediate their specific killing. In addition to their therapeutic capabilities, TCR-like antibodies are being developed as diagnostic reagents for cancer and infectious diseases, and serve as valuable research tools for studying MHC class I antigen presentation.

show abstract

Antibodies and Lentiviruses That Specifically Recognize a T Cell Epitope Derived from HIV-1 Nef Protein and Presented by HLA-C

Abstract: Material

Cited by 23 publications

References 43 publications

Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

An Inducible Cell-Cell Fusion System with Integrated Ability to Measure the Efficiency and Specificity of HIV-1 Entry Inhibitors

T-cell-receptor-like antibodies – generation, function and applications

Contact Info

Product

Resources

About