Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021345 (infectious mononucleosis)
 3,358 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral T lymphocytes from patients with infectious mononucleosis (IM) are sensitized in vivo against the Epstein-Barr virus (EBV). The expression of HLA-A, B, or C molecules at the target cell surface is necessary for the cytotoxic reaction because (a) EBV-positive Daudi cells lacking HLA-A, B, and C determinants are resistant to anti-EBV T-cell lysis, (b) cytolysis of EBV-positive target cells can be consistently inhibited by anti-HLA-A, B, and C and anti-beta 2 microglobulin antibodies. However, no evidence for allogeneic restriction in this system was apparent as (a) cytotoxic T lymphocytes (CTL) from one given individual could exert a cytotoxicity of a similar magnitude on different EBV-positive target cells, regardless of the number of HLA-A or B specificities shared by the effectors and targets; (b) CTL from IM patients were able to kill target cells without any HLA-A or B antigen in common; and (c) T5-1 variants lacking one or two HLA antigens at the A, B, or D locus are killed to the same extent as the parental cells. 7 of the 9 IM patients with detectable circulating anti-EBV CTL carried the HLA-A1 antigen, whereas none of the 16 IM patients lacking detectable peripheral CTL were HLA-A1 positive (mean specific lysis of T5-1 target cells by T cells from HLA-A1 positive patients: 29.3 vs. 0.6% in HLA-A1-negative patients) (P less than 10(-9)). These data suggest an HLA-A1-linked gene control of the magnitude of the anti-EBV CTL response. Thus, the HLA region appears to act at two different level sin the T-cell-mediated lysis of EBV-infected cells by controlling first, the development of anti-EBV and second, the expression of HLA-A, B, and C molecules involved as recognition structures at the target cell surface.
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PMID:Absence of allogeneic restriction in human T-cell-mediated cytotoxicity to Epstein-Barr virus-infected target cells. Demonstration of an HLA-linked control at the effector level. 22 86

In mice the cytotoxic T-cell response to several types of virus is influenced by genes within the major histocompatibility complex; in particular, genetic control is exercised at the effector cell level through a requirement that virus-specific cytotoxic T cells recognise viral antigens in association with H-2K and H=2D region gene products on the surface of infected cells. In man the restriction which the analogous HLA-A, -B and -C-region gene products might place on virus-specific T-cell function is still in dispute. The earliest and most controversial evidence concerns the Epstein-Barr virus (EBV), a B lymphotropic agent which causes infectious mononucleosis (IM) and which induces an unusually vigorous T-cell response; cytotoxic T cells from IM patients' blood were shown to be EBV-specific yet, in contrast to mouse systems, apparently free of any obvious HLA restriction. Since then T-cell recognition of EBV-infected B cells has assumed particular significance as a model system for the study of cytotoxic T-cell function in man. This report describes the results of a new approach clearly indicating that HLA-A and -B region products do indeed have a role in this system.
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PMID:HLA-restricted T-cell recognition of Epstein-Barr virus-infected B cells. 624 95

The frequency of HLA-A, -B and -DR antigens in 48 infectious mononucleosis (IM) patients was studied and the antigen frequencies were compared with those of a local panel. The resulting data do not confirm the association of IM and HLA-B35 as reported in a previous work. A high and significant frequency of blank HLA-DR phenotypes was noticed in IM population during the acute phase, but HLA-DR phenotypic expression was restored after recovery. This lack of expression could be the result of modified HLA-DR expression on circulating EBV infected B lymphocytes.
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PMID:HLA-AB and -DR types in patients with infectious mononucleosis (IM). 657 20

In immunocompetent individuals, the stability of the herpesvirus-host balance limits opportunities to study the disappearance of a virus-specific CD8(+) T-cell response. However, we noticed that in HLA-A 0201-positive infectious mononucleosis (IM) patients undergoing primary Epstein-Barr virus (EBV) infection, the initial CD8 response targets three EBV lytic antigen-derived epitopes, YVLDHLIVV (YVL), GLCTLVAML (GLC), and TLDYKPLSV (TLD), but only the YVL and GLC reactivities persist long-term; the TLD response disappears within 10 to 27 months. While present, TLD-specific cells remained largely indistinguishable from YVL and GLC reactivities in many phenotypic and functional respects but showed unique temporal changes in two markers of T-cell fate, interleukin 7 receptor alpha (IL-7Ralpha; CD127) and programmed death 1 (PD-1). Thus, following the antigen-driven downregulation of IL-7Ralpha seen on all populations in acute IM, in every case, the TLD-specific population recovered expression unusually quickly post-IM. As well, in four of six patients studied, TLD-specific cells showed very strong PD-1 upregulation in the last blood sample obtained before the cells' disappearance. Our data suggest that the disappearance of this individual epitope reactivity from an otherwise stable EBV-specific response (i) reflects a selective loss of cognate antigen restimulation (rather than of IL-7-dependent signals) and (ii) is immediately preceded, and perhaps mediated, by PD-1 upregulation to unprecedented levels.
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PMID:Upregulation of interleukin 7 receptor alpha and programmed death 1 marks an epitope-specific CD8+ T-cell response that disappears following primary Epstein-Barr virus infection. 1960 92

Epstein-Barr virus (EBV) infection, history of infectious mononucleosis (IM) and HLA-A and DRB1 have all been proposed as risk factors for multiple sclerosis (MS). Our aim was to analyse possible interactions between antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA1) or EBNA1 fragments, presence of DRB1*15 and absence of A*02. The study population includes newly diagnosed cases and matched controls. Interaction on the additive scale was calculated using attributable proportion due to interaction (AP), which is the proportion of the incidence among individuals exposed to two interacting factors that is attributable to the interaction per se. IM showed association with MS, odds ratio (OR)=1.89 (1.45-2.48% confidence interval (CI)), as did raised EBNA1 IgG OR=1.74 (1.38-2.18 95%CI). All EBNA1 fragment IgGs were associated with MS risk. However, EBNA1 fragment 385-420 IgG levels were more strongly associated to MS than total EBNA1 IgG, OR=3.60 (2.75-4.72 95%CI), and also interacted with both DRB1*15 and absence of A*02, AP 0.60 (0.45-0.76 95%CI) and AP 0.39 (0.18-0.61 95%CI), respectively. The observed interaction between HLA class I and II genotype and reactivity to EBV-related epitopes suggest that the mechanism through which HLA genes influence the risk of MS may, at least in part, involve the immune control of EBV infection.
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PMID:Epstein-Barr virus and multiple sclerosis: interaction with HLA. 2177 12

The Epstein-Barr virus (Human herpesvirus 4) encodes approximately 80 proteins, from which 15 possess at least 90 antigenic epitopes. Many of them stimulate the T cell receptors (TCR), but a few interact with the B cell receptors (BCR). Activation of B-cells and subsequent antibody production has not only been related to at least 3 envelope glycoproteins (mostly gp350) but also to latency associated membrane proteins (LMPs). The majority of EBV epitopes (over 80) inducing either cytotoxic and/or helper T lymphocytes were located on non-structural and/or latency associated polypeptides. The former interaction mediated by CD8plus/T cells is restricted by the HLA I molecules, predominantly of HLA-A subclass. In acute infectious mononucleosis (IM) patients (about 40 %) a considerable proportion of HLA B8 restricted CTL reactivity is directed against a single peptide (RAKFKQLL) of transactivator protein BZLF1/Zta. The EBV vaccines designed so far fall into two categories: those preventing any kind of infection (including prophylaxis of EBVassociated malignancies) and those designed for therapeutic purposes (to be used in subjects already infected). Preventive vaccines protecting against acute disease (such as IM) contain, as a rule, the gp350 polypeptide(s) encoded by the BLLF1 gene. Vaccines destined for tumor prevention rather consist of peptides derived from latency associated nuclear proteins (EBNA 2, 3 and 6) and/or from oncogenic latent membrane proteins (LMP1/LMP2a). Whereas the former generates antibodies preventing virus entry, the latter would potentiate the cell mediated response. In addition to recently described and purified individual recombinant immunogenic EBV polypeptides and/or their mixes, new perspectives were opened by construction of random overlapping strongly immunogenic scrambled polypeptide(s). Further novel approaches are based on carefully selected antigenic peptides (oligopeptides) coming from both, structural as well as non-structural or latencyassociated proteins bound to suitable carriers. Any constructs based on latency-associated proteins might be useful either for immunoprophylactic therapy following bone marrow and/or heart transplantations or for the prevention of EBVrelated tumors such as lymphomas and nasopharyngeal carcinoma. Due to the growing importance of the selected immunogenic epitopes as future vaccine components, at least the half of them has been patented not only as the natural amino acid sequence but also in different variations.
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PMID:Survey of Epstein Barr virus (EBV) immunogenic proteins and their epitopes: implications for vaccine preparation. 2516 57