Detection of viral superantigen–class II MHC interactions at the cell surface

Reilly, Melissa; Mix, Denise; Winslow, Gary M.

doi:10.1016/s0161-5890(01)00009-8

Cited by 3 publications

(4 citation statements)

References 15 publications

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“…Although mouse T cells are MHC class II negative and therefore do not present Mtv-8 on the cell surface, it is possible that Mtv-8 protein is present inside the cell and acts to chaperone the Vβ5 chain into the lysosomal degradation pathway, bypassing the plasma membrane [34, 35]. Delineating such an intracellular trafficking pattern would require use of Mtv-8-specific antibodies, and anti-Mtv reagents have been notoriously difficult to generate [36], although the apparent preference for superantigens in triggering TCR revision [20] is suggestive. Preferences in TCRα and TCRβ pairing have been well described [37-41], and it is possible that Vβ5 pairs poorly with the available TCRα chains, although the diversity of the TCRα repertoire in CD4 + T cells from Vβ5 Tg mice [4] renders this possibility unlikely.…”

Section: Discussionmentioning

confidence: 99%

Modulation of TCRβ surface expression during TCR revision

Simmons

Wubeshet

Ames

et al. 2012

Cellular Immunology

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TCR revision is a tolerance mechanism by which self-reactive TCRs expressed by mature CD4+ peripheral T cells are replaced by receptors encoded by genes generated by post-thymic DNA rearrangement. The down modulation of surface TCR expression initiates TCR revision, and serves as a likely trigger for the induction of the recombinase machinery. We show here in a Vβ5 transgenic mouse model system that downregulation of the self-reactive transgene-encoded TCR is not maintained by transgene loss or diminished transcription or translation. The downregulation of surface TCR expression likely occurs in two stages, only one of which requires tolerogen expression.

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Section: Discussionmentioning

confidence: 99%

Modulation of TCRβ surface expression during TCR revision

Simmons

Wubeshet

Ames

et al. 2012

Cellular Immunology

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“…through proteolytic processing (60). The nature of the active fragment remains ill defined; redundancy has been reported regarding the potency of the furin cleavage sites in activating vSAgs (61). Also, cathepsin L was shown to liberate a 27-kDa fragment, which could explain the activity of vSAgs in furin-deficient cells or after mutagenesis of the furin recognition motifs (62,63).…”

mentioning

confidence: 99%

“…Accordingly, it was later proposed that successful presentation of vSAg7 is conditional to the existence of a diverse, class II-bound peptide repertoire (71). Indeed, endogenous vSAg-induced T cell deletion was not taking place in modified mice expressing class II molecules almost exclusively loaded with CLIP (DM knockout (KO)) or loaded with a covalently linked peptide (E␣ [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] ). These results contrast with those obtained in vitro by Hsu et al (72), which suggest that class II-vSAg interactions occur in the ER through a CLIP-like region of vSAg occupying the peptide binding groove.…”

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confidence: 99%

A Defective Viral Superantigen-Presenting Phenotype in HLA-DR Transfectants Is Corrected by CIITA

Azar

Sékaly

Thibodeau

2005

The Journal of Immunology

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Activation of T lymphocytes by mouse mammary tumor virus superantigen (vSAg) requires binding to MHC class II molecules. The subcellular location where functional interactions occur between MHC class II molecules and vSAgs is still a matter of debate. To gain further insight into this issue, we have used human epithelial HeLa cells expressing HLA-DR1. Surprisingly, the human cells were unable to present transfected vSAg7 or vSAg9 to a series of murine T cell hybridomas. The defect is not related to a lack of vSAg processing, because these cells can indirectly activate T cells after coculture in the presence of B lymphocytes. However, after IFN-γ treatment, the HeLa DR1+ cells became apt at directly presenting the vSAg. Furthermore, transfection of CIITA was sufficient to restore presentation. Reconstitution experiments demonstrated the necessity of coexpressing HLA-DM and invariant chain (Ii) for efficient vSAg presentation. Interestingly, inclusion of a dileucine motif in the DRβ cytoplasmic tail bypassed the need for HLA-DM expression and allowed the efficient presentation of vSAg7 in the presence of Ii. A similar trafficking signal was included in vSAg7 by replacing its cytoplasmic tail with the one of Ii. However, sorting of this chimeric Ii/vSAg molecule to the endocytic pathway completely abolished both its indirect and direct presentation. Together, our results suggest that functional vSAgs-DR complexes form after the very late stages of class II maturation, most probably at the cell surface.

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“…Neurotropic viruses can also cause direct tissue/myelin damage, resulting in sensitization of autoreactive T cells in response to myelin breakdown products/antigens. Furthermore, viral infections of the central nervous system can also induce autoimmune responses through epitope spreading (27) and superantigen activity (33,40,43). However, to date the issues related to the etiologic role of virus in MS remain unresolved.…”

mentioning

confidence: 99%

Detection of Viral DNA and Immune Responses to the Human Herpesvirus 6 101-Kilodalton Virion Protein in Patients with Multiple Sclerosis and in Controls

Tejada‐Simon

Zang

Hong

et al. 2002

J Virol

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Human herpesvirus 6 (HHV-6), a latent lymphotropic and neurotropic virus, has been suspected as an etiologic agent in multiple sclerosis (MS). The study was undertaken to correlate virologic evidence for HHV-6 activity with the state of host immunity to HHV-6 in MS patients and control subjects. The study revealed that cell-free DNA of HHV-6 was detected more frequently in both serum and cerebrospinal fluid of MS patients than in those of control subjects. T cells recognizing the recombinant 101-kDa protein (101K) corresponding to the major immunoreactive region unique to HHV-6 occurred at significantly lower precursor frequency in MS patients than in control subjects. The resulting HHV-6-specific T-cell lines obtained from MS patients exhibited skewed cytokine profiles characterized by the inability to produce interleukin-4 (IL-4) and IL-10. The decreased T-cell responses to HHV-6 and the altered cytokine profile were consistent with significantly declined serum immunoglobulin G (IgG) titers for HHV-6 of MS patients compared to those of control subjects. In contrast, elevated serum IgM titers for HHV-6 were detected in the majority of MS patients, which may reflect frequent exposure of B cells to HHV-6. The findings suggest that the decreased immune responses to HHV-6 may be responsible for ineffective clearance of HHV-6 in MS patients.

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Detection of viral superantigen–class II MHC interactions at the cell surface

Cited by 3 publications

References 15 publications

Modulation of TCRβ surface expression during TCR revision

Modulation of TCRβ surface expression during TCR revision

A Defective Viral Superantigen-Presenting Phenotype in HLA-DR Transfectants Is Corrected by CIITA

Detection of Viral DNA and Immune Responses to the Human Herpesvirus 6 101-Kilodalton Virion Protein in Patients with Multiple Sclerosis and in Controls

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