Epstein-Barr virus Peptide Presented by HLA-E is Predominantly Recognized by CD8bright Cells in multiple Sclerosis Patients

Jørgensen, Pernille B.; Livbjerg, Astrid H.; Hansen, Hans J.; Petersen, Thor; Höllsberg, Per

doi:10.1371/journal.pone.0046120

Cited by 39 publications

(28 citation statements)

References 52 publications

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“…74 Similarly, HLA-E restricted CD8+ CTLs specific for viral and bacterial peptides presented in HLA-E can be generated and mediate direct cytotoxicity against infected target cells. 75–77 These data demonstrate that viral infections of placental tissue may alter the HLA expression profile of infected trophoblast cells and render them susceptible to NK cell killing or lysis by HLA-C or HLA-E restricted CD8+ T cells (Fig. 1g-h).…”

Section: Antigen Specificity Of Cd8+ T Cells During Pregnancymentioning

confidence: 74%

“…74 h) Similar to (g), HLA-E molecules expressed on fetal EVT cells have been shown able to present viral and bacterial peptides to Ag-specific CD8+ T cells. [75][76][77] TCR. [40][41][42] Cross-reactivity was shown against a wide variety of HLA-A, HLA-B, and MHC class II molecules and it cannot be ruled out that virus-specific and HLA-C cross-reactive T cells exist.…”

Section: Direct Mhc Recognition During Pregnancymentioning

confidence: 99%

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CD8+ Effector T Cells at the Fetal–Maternal Interface, Balancing Fetal Tolerance and Antiviral Immunity

Tilburgs

Strominger

2013

American J Rep Immunol

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During pregnancy CD8+ effector T cells need optimal immune regulation to prevent a detrimental response to allogeneic fetal cells while providing immune protection to infections. A significant proportion of (prospective) mothers carry naïve or memory CD8+ T cells with a TCR that can directly bind to paternal MHC molecules. In addition, a high percentage of pregnant women develop specific T cell responses to fetal minor histocompatibility antigens (mHags). Under normal conditions, fetal–maternal MHC and mHag mismatches lead to elevated lymphocyte activation but do not induce pregnancy failure. Furthermore, viral infections alter the maternal CD8+ T cell response by changing the CD8+ T cell repertoire and increasing the influx of CD8+ T cells to decidual tissue. The normally high T cell activation threshold at the fetal–maternal interface may prevent efficient clearance of viral infections. Conversely, the increased inflammatory response due to viral infections may break fetal–maternal tolerance and lead to pregnancy complications. The aim of this review is to discuss the recent studies of CD8+ T cells in pregnancy, identify potential mechanisms for antigen-specific immune recognition of fetal extravillous trophoblast (EVT) cells by CD8+ T cells, and discuss the impact of viral infections and virus-specific CD8+ T cells during pregnancy.

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Section: Antigen Specificity Of Cd8+ T Cells During Pregnancymentioning

confidence: 74%

Section: Direct Mhc Recognition During Pregnancymentioning

confidence: 99%

CD8+ Effector T Cells at the Fetal–Maternal Interface, Balancing Fetal Tolerance and Antiviral Immunity

Tilburgs

Strominger

2013

American J Rep Immunol

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“…The function of these CD8 subpopulations might differ. 15,16 Increased levels of CD8 dim suggest an immunosuppressed state 17 and cytotoxic T-lymphocyte (CTL) impairment, 18 and have been associated with disease progression in human immunodeficiency virus (HIV)-positive patients. 19 Perforin (PRF) and granzyme B (GZB) are cytotoxic granules that mediate cell death.…”

Section: Introductionmentioning

confidence: 99%

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Luetragoon

Rutqvist²,

Tangvarasittichai

et al. 2018

Immunology

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Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking-related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty-four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never-users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C-reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8 cells in the lymphocyte group, CD13 CD11 , CD13 CD14 , CD13 CD56 cells in the monocyte group and CD13 CD11 , CD13 CD56 cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8 GZB cells in the CD8 group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking-related disease and the variations observed in clinical outcomes.

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“…Engagement of the highly expressed CD94/NKG2A by the HLA-E/b2m/HLA-class I signal peptide complex reduces NK cell-mediated killing, thus enabling NK cells to monitor the HLA-class I expression, which is often down-modulated following cell transformation or viral infection [14]. More recently, novel self- [15,16] or pathogen-derived peptides [17][18][19][20][21] have been identified as binders of HLA-E molecules. Evidence has also been provided that HLA-E, like the murine homolog Qa-1, can interact directly with TCRs on CD8 + T cells with cytotoxic [22][23][24][25] or regulatory [26][27][28] functions.…”

Section: Introductionmentioning

confidence: 99%

Regulation and trafficking of the HLA-E molecules during monocyte-macrophage differentiation

Camilli¹,

Cassotta²,

Battella³

et al. 2015

Journal of Leukocyte Biology

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HLA-E is a nonclassical HLA-class I molecule whose best known role is to protect from the natural killer cells. More recently, an additional function more similar to that of classical HLA-class I molecules, i.e., antigen presentation to T cells, is emerging. However, much remains to be explored about the intracellular trafficking of the HLA-E molecules. With the use of 3 different cellular contexts, 2 monocytic cell lines, U937 and THP1, and peripheral blood monocytes, we show here a remarkable increase of HLA-E during monocyte-macrophage differentiation. This goes independently from the classical HLA-class I, the main source of HLA-E-specific peptides, which is found strongly up-regulated upon differentiation of peripheral blood monocytes but not at all in the case of U937 and THP1 cell lines. Although in all cases, there was a moderate increase of HLA-E expressed in the cell surface, lysis by natural killer cells is comparably restored by an anti-NKG2A antibody in untreated as well as in PMA-differentiated U937 cells. Instead, the great majority of the HLA-E is retained in the vesicles of the autophagy-lysosome network, where they colocalize with the microtubule-associated protein light chain 3, as well as with the lysosomal-associated membrane protein 1. We conclude that differently from the classical HLA-class I molecules, the primary destination of the newly synthesized HLA-E molecules in macrophages is, rather than the cell membrane, the intracellular autophagy-lysosomal vesicles where they are stored and where they can encounter the exogenous antigens.

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Epstein-Barr virus Peptide Presented by HLA-E is Predominantly Recognized by CD8bright Cells in multiple Sclerosis Patients

Cited by 39 publications

References 52 publications

CD8+ Effector T Cells at the Fetal–Maternal Interface, Balancing Fetal Tolerance and Antiviral Immunity

CD8+ Effector T Cells at the Fetal–Maternal Interface, Balancing Fetal Tolerance and Antiviral Immunity

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Regulation and trafficking of the HLA-E molecules during monocyte-macrophage differentiation

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