scholarly journals Development of Epstein-Barr virus-specific memory T cell receptor clonotypes in acute infectious mononucleosis.

1996 ◽  
Vol 184 (5) ◽  
pp. 1815-1824 ◽  
Author(s):  
S L Silins ◽  
S M Cross ◽  
S L Elliott ◽  
S J Pye ◽  
S R Burrows ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Cell Receptor ◽  
Memory T Cell ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
Acute Infectious Mononucleosis

The importance of cytotoxic T lymphocytes (CTLs) in the immunosurveillance of Epstein-Barr virus (EBV)-infected B cells is firmly established, and the viral antigens of CTL recognition in latent infection are well defined. The epitopes targeted by CTLs during primary infection have not been identified, however, and there is only limited information about T cell receptor (TCR) selection. In the present report, we have monitored the development of memory TCR-beta clonotypes selected in response to natural EBV infection in a longitudinal study of an HLA-B8+ individual with acute infectious mononucleosis (IM). By stimulating peripheral blood lymphocytes with HLA-B8+ EBV-transformed B lymphoblastoid cells, the primary virus-specific CTL response was shown to include specificities for two HLA-B8-restricted antigenic determinants, FLRGRAYGL and QAKWRLQTL, which are encoded within the latent EBV nuclear antigen EBNA-3. TCR-beta sequence analysis of CTL clones specific for each epitope showed polyclonal TCR-beta repertoire selection, with structural restrictions on recognition that indicated antigen-driven selection. Furthermore, longitudinal repertoire analysis revealed long-term preservation of a multiclonal effector response throughout convalescence, with the reemergence of distinct memory T cell clonotypes sharing similar structural restrictions. Tracking the progression of specific TCR-beta clonotypes and antigen-specific TCR-V beta family gene expression in the peripheral repertoire ex vivo using semiquantitative PCR strongly suggested that selective TCR-beta expansions were present at the clonotype level, but not at the TCR-V beta family level. Overall, in this first analysis of antigen-specific TCR development in IM, a picture of polyclonal TCR stimulation is apparent. This diversity may be especially important in the establishment of an effective CTL control during acute EBV infection and in recovery from disease.

scholarly journals Epitope-dependent Selection of Highly Restricted or Diverse T Cell Receptor Repertoires in Response to Persistent Infection by Epstein-Barr Virus

1997 ◽  
Vol 186 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Pedro-Otavio de Campos-Lima ◽  
Victor Levitsky ◽  
Martha P. Imreh ◽  
Riccardo Gavioli ◽  
Maria G. Masucci
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Epstein Barr Virus ◽  
Cell Receptor ◽  
Nuclear Antigen ◽  
Alanine Scanning Mutagenesis ◽  
Barr Virus ◽  
High Affinity ◽  
Epstein Barr ◽  
Complementarity Determining Regions

The T cell receptor (TCR) repertoires of cytotoxic responses to the immunodominant and subdominant HLA A11–restricted epitopes in the Epstein-Barr virus (EBV) nuclear antigen-4 were investigated in four healthy virus carriers. The response to the subdominant epitope (EBNA4 399-408, designated AVF) was highly restricted with conserved Vβ usage and identical length and amino acid motifs in the third complementarity-determining regions (CDR3), while a broad repertoire using different combinations of TCR-α/β V and J segments and CDR3 regions was selected by the immunodominant epitope (EBNA4 416-424, designated IVT). Distinct patterns of interaction with the A11–peptide complex were revealed for each AVF- or IVT-specific TCR clonotype by alanine scanning mutagenesis analysis. Blocking of cytotoxic function by antibodies specific for the CD8 coreceptor indicated that, while AVF-specific TCRs are of high affinity, the oligoclonal response to the IVT epitope includes both low- and high-affinity TCRs. Thus, comparison of the memory response to two epitopes derived from the same viral antigen and presented through the same MHC class I allele suggests that immunodominance may correlate with the capacity to maintain a broad TCR repertoire.

SH2D1A mutations in Japanese males with severe Epstein-Barr virus–associated illnesses

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 1268-1270 ◽  
Author(s):  
Ryo Sumazaki ◽  
Hirokazu Kanegane ◽  
Maki Osaki ◽  
Takashi Fukushima ◽  
Masahiro Tsuchida ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Genetic Disorder ◽  
Lymphoproliferative Disease ◽  
Barr Virus ◽  
Ebv Infection ◽  
Sporadic Cases ◽  
Epstein Barr ◽  
Acute Infectious Mononucleosis

X-linked lymphoproliferative disease (XLP), a genetic disorder characterized by immunodeficiency to Epstein-Barr virus (EBV) infection, has been linked to mutations in the SH2D1A gene. To search for the occurrence of SH2D1A mutations in Japan, we performed genetic analysis of the SH2D1A gene in 40 males presenting with severe EBV-associated illnesses, including fulminant infectious mononucleosis, EBV-positive lymphoma, and severe chronic active EBV infection. SH2D1A mutations were detected in 10 of these 40 patients. Five of these 10 cases were sporadic. Patients with SH2D1A mutations displayed severe acute infectious mononucleosis with hyperimmunoglobulin M, hypogammaglobulinemia, and B-cell malignant lymphoma. By contrast, chronic active EBV infection was not associated with SH2D1Amutations. XLP survivors exhibited normal levels of circulating EBV-DNA during convalescence, suggesting that SH2D1A protein is not directly responsible for control of EBV replication. Thus, genetic analysis of the SH2D1A gene is particularly useful in the diagnosis of sporadic cases and carriers of XLP.

scholarly journals Targeting Epstein-Barr virus–transformed B lymphoblastoid cells using antibodies with T-cell receptor–like specificities

Blood ◽  
2016 ◽  
Vol 128 (10) ◽  
pp. 1396-1407 ◽  
Author(s):  
Junyun Lai ◽  
Wei Jian Tan ◽  
Chien Tei Too ◽  
Joanna Ai Ling Choo ◽  
Lan Hiong Wong ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
T Cell Receptor ◽  
Epstein Barr Virus ◽  
Cell Receptor ◽  
Barr Virus ◽  
Key Points ◽  
Tumor Load ◽  
Epstein Barr

Key Points Anti-EBV TCR-like monoclonal antibodies reduce BLCLs tumor load in vivo. Anti-EBV TCR-like monoclonal antibodies mediate phagocytosis of BLCLs by macrophages.

scholarly journals Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 744-750 ◽  
Author(s):  
I Anagnostopoulos ◽  
M Hummel ◽  
C Kreschel ◽  
H Stein
Keyword(s):  
Epithelial Cells ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Lymphoid Cells ◽  
Productive Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Infected Cells ◽  
Epstein Barr ◽  
Acute Infectious Mononucleosis

The present study was undertaken to unequivocally demonstrate the morphology, immunophenotype, and localization of Epstein Barr virus (EBV)-infected cells as well as the type of infection (latent versus productive) in tonsils of acute infectious mononucleosis. Paraffin sections from nine cases with clinical, serologic, and morphologic evidence of EBV infection were analyzed for the detection of small transcripts, designated EBER1 & 2, and BHLF1 by in situ hybridization (ISH) using nonisotopically labeled probes. ISH was combined with immunohistology, employing a broad panel of antibodies against B-, T-, epithelial-, macrophage-, and follicular dendritic cell (FDC)-antigens. All EBER-positive cells could be identified as lymphocytes, as they did not exhibit any morphologic or immunologic characteristics of epithelial cells, macrophages, or FDCs. A preferential accumulation of EBER-positive cells was noted around crypts, within surface squamous epithelium, and in the surroundings of necrosis. The majority of these lymphocytes could be shown to be B cells, which morphologically included Reed-Sternberg (RS)-like cells, immunoblasts, medium-sized lymphoid cells, as well as cells with plasmacytoid differentiation. In all cases, a varying number of EBER-positive T cells could be identified. ISH for BHLF1-RNA detection showed that almost all cases contained single positive small lymphoid cells, indicating a transition from latent to productive infection cycle. Such cells could also be detected within the crypt epithelium reaching up to its surface. Additional screening of 123 oropharyngeal mucosa samples from patients without evidence of acute EBV-infection, using the polymerase chain reaction for EBV-DNA detection combined with EBER- and BHLF1-ISH showed single latently infected lymphocytes in only one case. Our data imply that infected lymphocytes and not epithelial cells are, in fact, the reservoir for EBV infection, and that these are the cells that participate in the interindividual virus transfer.

T-cell receptor gene rearrangement in Epstein–Barr virus infectious mononucleosis

2011 ◽  
Vol 29 (3) ◽  
pp. 2300-2302 ◽  
Author(s):  
L. Marbello ◽  
M. Riva ◽  
S. Veronese ◽  
A. M. Nosari ◽  
E. Ravano ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Epstein Barr Virus ◽  
Gene Rearrangement ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Barr Virus ◽  
T Cell Receptor Gene ◽  
Epstein Barr ◽  
Cell Receptor Gene
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