Functional Evaluation of HIV/SIV Nef as Superantigen

Lapatschek, Matthias; Dürr, Susanne; Sutter, Gerd; Wagner, Hermann; Miethke, Thomas

doi:10.1006/viro.2001.0844

Cited by 3 publications

(4 citation statements)

References 42 publications

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“…Gp120 has been reported to have a superantigen activity for a subset of IgVH3 expressing B cells [15] and certain synthetic HIV peptides for both CD4+and CD8+ T cells [16]. However, others have shown no superantigenic activity with HIV proteins [17] and it is now the general consensus that superantigens in HIV infection play little role in T cell expansions in vivo .…”

Section: Discussionmentioning

confidence: 99%

T cell receptor usage in patients with non-progressing HIV infection

Bodman‐Smith

Williams²,

Johnstone³

et al. 2002

Clinical and Experimental Immunology

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SUMMARY It is still unclear why some patients with HIV progress more slowly than others to developing full blown AIDS. In this study using flow cytometry we have investigated the TCRBV repertoire of peripheral blood T lymphocytes in 17 long‐term non‐progressing HIV patients (LTNP) to determine if there is a biased usage of T cell receptor V gene products. Patients were identified from hospital records and entered into the study. Three colour flow cytometry was used to determine the expression of the TCRBV3S5, BV5S1, BV5S2, BV5S3, BV6S1, BV7S1, BV9, BV11, BV12, BV13, BV14, BV16, BV17, BV18, BV20, BV21S3, BV22, and BV23 by CD8 and CD4 positive cells isolated from the peripheral blood of patients and controls. Increases in the absolute numbers of CD8+ T cells expressing TCRBV2 and 8 were observed in the HIV‐LTNP population (P < 0·05 in both cases). No differences were seen in numbers of CD8+ T cells expressing other TCRBV or in any TCRBV within the CD4+ T cell popu‐lation. At follow up (1–2 years later), those patients in which CD4 levels were below 500 × 106/l were those initially found to have lower levels of TCRBV8 +ve CD8 cells. A significant increase in the absolute numbers of T cells coexpressing the gamma delta (γδ) T cell receptor and CD8 were also seen in the HIV‐LTNP patients compared with controls (P = 0·002). The increase in CD8+ T cells in the HIV‐LTNP patients may be interpreted as either an antigen specific, or group of antigen specific responses to viral antigen, or less likely a viral superantigen. A low level of TCRBV8, CD8+ T cells might be predictive of a more rapid disease progression and might indicate a protective role for this population in HIV infected patients. The increase in γδT cells bearing the CD8 coreceptor suggests a role for this cell type in the response to HIV infection.

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Section: Discussionmentioning

confidence: 99%

T cell receptor usage in patients with non-progressing HIV infection

Bodman‐Smith

Williams²,

Johnstone³

et al. 2002

Clinical and Experimental Immunology

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“…It is believed that, the massive activation of CD4 + T cells (selectively with Vβ-12 + , Vβ-5.3 + and Vβ-18 + TCRs) in early stages of infection and clonal deletion, anergy and apoptosis of bystander T cells in the late stages may be due to SAg property of Nef protein, as well as the other mechanisms. However there are some studies indicating that Nef does not act as a SAg (Lapatschek, et al 2001). HIV gp120 glycoprotein is a B-cell SAg that binds to VH3-expressing B cell receptors and causes polyclonal B cell activation.…”

Section: Mi̇krobi̇yoloji̇ Bülteni̇mentioning

confidence: 99%

“…AIDS'de ortaya çıkan klinik semptomların bireysel farklılıklar göstermesinin, TCR Vβ gen polimorfi zmlerine ve MHC-II alellerinin SAg'e karşı afi nitesindeki farklılıklara bağlı olduğu düşünülmektedir 42 . Buna karşın Lapatschek ve arkadaşları 46 , Nef'in fonksiyonel olarak SAg gibi davranmadığını ileri sürmektedir.…”

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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“…The HIV‐1‐encoded proteins included gp12033 and HIV‐1 “nef”. 34 While the mechanisms by which HIV gp120 serves as a superantigen have been defined primarily in terms of the ability of the gp120 molecule to bind selectively to the VH3 Ig gene‐encoding family and to B cells that express VH3 Ig,35 the ability of the HIV‐1‐encoded “nef” gene has been somewhat controversial 36. Some studies have also documented polyclonal B cell activation as a consequence of HIV‐1 infection and have reasoned this activity to lead to hypergammaglobulinemia, which has been well characterized in HIV‐1‐infected individuals 37.…”

Section: Potential Mechanisms Implicated In the Autoimmunity Of Hiv‐1mentioning

confidence: 99%

Human and Nonhuman Primate Lentiviral Infection and Autoimmunity

Onlamoon

Pattanapanyasat

Ansari

2005

Annals of the New York Academy of Sciences

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The goal of this communication is to summarize the following-the types of autoimmune responses that have been characterized in human HIV-1 infection; the potential mechanisms that were initially thought to be the basis for such autoimmune responses; the prevalence and incidence of conventional autoimmune diseases with HIV-1 infection; the spectrum of autoimmune disorders following the institution of HAART and its associated mechanisms; the role of such autoimmunity in SIV-infected nonhuman primates; and the molecular basis for autoimmune responses, such as the role of exosomes in lentiviral disease.

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Functional Evaluation of HIV/SIV Nef as Superantigen

Cited by 3 publications

References 42 publications

T cell receptor usage in patients with non-progressing HIV infection

T cell receptor usage in patients with non-progressing HIV infection

Viral Superantigens

Human and Nonhuman Primate Lentiviral Infection and Autoimmunity

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