Vβ Activation by HIV Nef Protein: Detection by a Simple Amplification Procedure

Tanabe, Taishi; Torres, Barbara A.; Subramaniam, Prem S.; Johnson, Howard M.

doi:10.1006/bbrc.1996.5991

Cited by 13 publications

(4 citation statements)

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“…An HIV-encoded superantigen has been identified (18). Nef, a regulatory protein expressed early in the infection of CD4+ T cells, was shown to induce VI3-specificT-cell proliferation in the absence of processing (18,88). T-cell proliferation required the presence of antigen-presenting cells.…”

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Superantigens: The Good, the Bad, and the Ugly

Torres

Kominsky

Perrin

et al. 2001

Exp Biol Med (Maywood)

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Increasing evidence suggests that superantlgens playa role In Immune-mediated diseases. Superantlgens are potent activators of CD4+T cells, causing rapid and massive proliferation of cells and cytoklne production. This characteristic of auperarmgens can be exploited In diseases where strong Immunologic responses are required, such as In the B16F10 animal model of melanoma. Superantlgen administration Is able to significantly enhance Ineffective anti-tumor Immune responses, resulting in potent and long-lived protective anti-tumor Immunity. However, superantlgens are more well-known for the role they play in diseases. Studies using an animal model for neurologic demyelinating diseases such as multiple sclerosis show that superantlgens can Induce severe relapses and activate autoreactive T cells not Involved In the Initial bout of disease. This may also Involve epltope spreading of disease. Superantigens have also been Implicated In acute diseases such as food poisoning and TSS, and In chronic diseases such as psoriasis and rheumatoid arthritis. Viral superantigens are also Involved In the disease process, Including superantigens derived from human Immunodeficiency virus and mouse mammary tumor virus. Finally, Immunotherapies that ameliorate the role played by superantigens In disease are discussed.

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confidence: 99%

Superantigens: The Good, the Bad, and the Ugly

Torres

Kominsky

Perrin

et al. 2001

Exp Biol Med (Maywood)

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“…Initial screening was performed using a simple amplification procedure to detect V␤ expansion (32), and a panel of monoclonal antibodies was selected for use in the subsequent cytometric analysis. V␤ expression of stimulated PBMC after coculture with different bacteria for 72 h was determined by flow cytometric analysis (FACSort flow cytometer; Becton Dickinson, San Jose, Calif.) using a fluorescein-labeled, CD4 ϩ -T-cellspecific monoclonal antibody (Becton Dickinson) and a panel of rhodamine-labeled, anti-V␤ antibodies (Becton Dickinson).…”

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Prevotella intermedia Stimulates Expansion of Vβ-Specific CD4 ⁺ T Cells

Leung

Torres

2000

Infect Immun

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Recent evidence suggests that certain periodontal pathogens preferentially stimulate T cells expressing specific variable regions on the ␤ chain (V␤) of the T-cell receptor, which may indicate the presence of a superantigen. Superantigens are microbial proteins that activate large numbers of CD4 ؉ T cells in a V␤-specific manner. The purpose of this study was to determine whether Prevotella intermedia, a putative periodontal pathogen, activates populations of specific V␤ on CD4 ؉ T cells. Among the bacterial strains tested, P. intermedia strain 17, a clinical isolate, induced the strongest proliferative response in peripheral blood mononuclear cells. Antibodies raised against whole cells of this organism blocked the proliferative activity. P. intermedia-induced proliferation was T-cell specific and required the presence of antigen-presenting cells. Flow cytometric analysis showed that CD4 ؉ T-cell subsets expressing V␤8, V␤12, and V␤17 expanded in response to P. intermedia strain 17. The ability of P. intermedia to stimulate CD4؉ -T-cell proliferation was further supported by the production profiles of key T-cell cytokines, gamma interferon and interleukin-2. The data collectively suggest that certain strains of P. intermedia can activate V␤-specific T cells in a manner similar to that of other known microbial superantigens.

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“…Nef'in sebep olduğu T hücre aktivasyonunun, SAg özelliğine bağlı olabileceği düşünülmektedir. Nef, enfeksiyonun erken döneminde, M-tropik HIV ile enfekte makrofajlardan salınmakta ve seçici olarak Vβ5, 8, 12-18 TCR taşıyan CD4 + T hücrelerini aktive etmektedir 12,44 . Böylece dinlenme halindeki CD4 + T hücrelerinin masif aktivasyonu ve proliferasyonu gerçekleşmekte; yani virus, replike olabilmek için kendisine bol miktarda aktive T hücre havuzu oluşmaktadır 45 .…”

Section: Hiv Ile İlişkili Süperantijenlerunclassified

Viral Superantigens

US¹

2016

Mikrobiyol Bul

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Superantigens (SAgs) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of T cells via an unconventional mechanism. They cause polyclonal activation of T cells in a non-specific manner, by binding to a particular variable-beta (Vβ) chain of T-cell receptor (TCR) and MHC class II molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the T cell. SAgs are classified into three groups, namely 1) exogenous (soluble proteins and exotoxins secreted by microorganisms), 2) endogenous (transmembrane proteins encoded by viruses which are integrated into the genome) and 3) B-cell SAgs (proteins which stimulate predominantly B cells). The best characterized and mostly studied SAgs are staphylococcal and streptococcal exotoxins, however it is well-known that many other microorganisms also possess SAg activities. Despite the presence of several viruses that cause severe infections in humans, the number of viruses that have proteins identified with SAg property in their pathogenesis, is relatively low. To date, the defined viruses that encoded SAgs are as follows; mouse mammary tumor virus (MMTV) (Marrack, et al. 1991), rabies virus (Lafon, et al. 1992), Epstein-Barr virus (EBV) (Sutkowski, et al. 1996), human endogenous retrovirus (HERV) (Conrad, et al. 1997), human immunodeficiency virus (HIV) (Posnett, et al. 1995; Torres, et al. 1996; Townsley-Fuchs, et al. 1997) and Ebola virus (Leroy, et al. 2011). SAgs were first described in the MMTV, a polymorphic B-type retrovirus that is either contained in the genome as an endogenous provirus (germline transmission) or exogenous infectious virus that transmits vertically via breast milk. Both MMTV forms encode SAgs. The SAg-mediated massive T cell activation is required for the spread of exogenous MMTV from intestines to mammary glands, facilitating the transmission of infectious virus. On the other hand, expression of endogenous SAgs leads to thymic deletion of responding T cells (bearing Vβ6-9+ TCR) due to self-tolerance induction during the fetal life, and protects the host against future exogenous MMTV infections. The SAg of rabies virus is the N protein found in nucleocapsid structure and stimulates Vβ8+TCR-bearing T cells. The SAg-induced polyclonal activation of T cells leads to turn-off the specific immune response, to enhance the immunopathogenesis and facilitates viral transmission from the initial site of infection (the muscle tissue) to the nerve endings. In case of EBV-associated SAg that activates Vβ13+TCR-bearing T cells, it was detected that the SAg activity was not encoded by EBV itself, but instead was due to the transactivation of HERV-K18 by EBV latent membrane proteins, whose env gene encodes the SAg (Sutkowski, et al. 2001). It has been denoted that EBV-induced SAg expression plays a role in the long-term persistence and latency of virus in memory B cells, in the development of autoimmune diseases and in the oncogenesis mechanisms. The prote...

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Vβ Activation by HIV Nef Protein: Detection by a Simple Amplification Procedure

Cited by 13 publications

References 20 publications

Superantigens: The Good, the Bad, and the Ugly

Superantigens: The Good, the Bad, and the Ugly

Prevotella intermedia Stimulates Expansion of Vβ-Specific CD4 ⁺ T Cells

Viral Superantigens

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Vβ Activation by HIV Nef Protein: Detection by a Simple Amplification Procedure

Cited by 13 publications

References 20 publications

Superantigens: The Good, the Bad, and the Ugly

Superantigens: The Good, the Bad, and the Ugly

Prevotella intermedia Stimulates Expansion of Vβ-Specific CD4 + T Cells

Viral Superantigens

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Prevotella intermedia Stimulates Expansion of Vβ-Specific CD4 ⁺ T Cells