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

Content Provider	PubMed Central
Author	Jørgensen, Pernille B. Livbjerg, Astrid H. Hansen, Hans J. Petersen, Thor Per, Höllsberg
Editor	Jacobson, Steven
Copyright Year	2012
Abstract	Multiple sclerosis (MS) is associated with Epstein-Barr virus (EBV) infection, but impaired immune suppression may be part of the disease pathogenesis. CD8+ T cells that are restricted by HLA-E exert an important immunoregulatory mechanism. To explore how EBV might interfere with immune regulation, we examined the expression of HLA-E and the frequency of CD8+ cells recognizing HLA-E, presenting either an EBV peptide from the BZLF1 protein or a signal sequence peptide from HLA-A2, in relapsing remitting (MS-RR), primary progressive (MS-PP) MS patients, and healthy controls (HC). Treatment with IFN-α or EBV increased HLA-E expression on CD4+ cells. However, only MS-PP had increased expression of HLA-E on resting CD4+ cells when compared with HC (p<0.005). CD8+ cells were divided into CD8bright and CD8dim cells by flow cytometry analyses. MS-RR had significantly fewer CD8dim cells than HC (p<0.003). Flow cytometry analyses were performed with HLA-E tetramers folded in the presence of the EBV or HLA-A2 peptide to identify HLA-E-interacting cells. MS-RR had increased frequency of CD8bright cells recognizing HLA-E/A2 (p = 0.006) and HLA-E/BZLF1 (p = 0.016). Conversely, MS-RR had fewer CD8dim cells that recognized HLA-E/BZLF1 (p = 0.001), but this could be attributed to the overall lower number of CD8dim cells in MS-RR. Whereas HLA-E/A2 was predominantly recognized by CD8dim cells, HLA-E/BZLF1 was predominantly recognized by CD8bright cells in MS-RR and MS-PP, but not in HC. As expected, HLA-E/A2 was also recognized by CD8-negative cells in a CD94-dependent manner, whereas HLA-E/BZLF1 was poorly recognized in all groups by CD8-negative cells. These data demonstrate that MS-RR patients have expanded their CD8bright cells recognizing HLA-E/BZLF1. Moreover, HLA-E/BZLF1 appears to be recognized by the immune system in a different manner than HLA-E/A2.
Related Links	http://dx.doi.org/10.1371/journal.pone.0046120
Starting Page	46120
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	9
Volume Number	7
Language	English
Publisher	Public Library of Science
Publisher Date	2012-09-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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