scholarly journals Direct Visualization of Antigen-specific CD8+T Cells during the Primary Immune Response to Epstein-Barr Virus In Vivo

1998 ◽  
Vol 187 (9) ◽  
pp. 1395-1402 ◽  
Author(s):  
M.F.C. Callan ◽  
L. Tan ◽  
N. Annels ◽  
G.S. Ogg ◽  
J.D.K. Wilson ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Epstein Barr Virus ◽  
T Cell Response ◽  
Primary Immune Response ◽  
Barr Virus ◽  
Epstein Barr

Primary infection with virus can stimulate a vigorous cytotoxic T cell response. The magnitude of the antigen-specific component versus the bystander component of a primary T cell response remains controversial. In this study, we have used tetrameric major histocompatibility complex–peptide complexes to directly visualize antigen-specific cluster of differentration (CD)8+ T cells during the primary immune response to Epstein-Barr virus (EBV) infection in humans. We show that massive expansion of activated, antigen-specific T cells occurs during the primary response to this virus. In one individual, T cells specific for a single EBV epitope comprised 44% of the total CD8+ T cells within peripheral blood. The majority of the antigen-specific cells had an activated/memory phenotype, with expression of human histocompatibility leukocyte antigen (HLA) DR, CD38, and CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of CD45RA. After recovery from AIM, the frequency of antigen-specific T cells fell in most donors studied, although populations of antigen-specific cells continued to be easily detectable for at least 3 yr.

scholarly journals T Cell Epitope Clustering in the Highly Immunogenic BZLF1 Antigen of Epstein-Barr Virus

2014 ◽  
Vol 89 (1) ◽  
pp. 703-712 ◽  
Author(s):  
Melissa J. Rist ◽  
Michelle A. Neller ◽  
Jacqueline M. Burrows ◽  
Scott R. Burrows
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Epstein Barr Virus ◽  
T Cell Response ◽  
T Cell Epitopes ◽  
Barr Virus ◽  
Epstein Barr ◽  
Hla Molecules

ABSTRACTPolymorphism in the human leukocyte antigen (HLA) loci ensures that the CD8+T cell response to viruses is directed against a diverse range of antigenic epitopes, thereby minimizing the impact of virus escape mutation across the population. The BZLF1 antigen of Epstein-Barr virus is an immunodominant target for CD8+T cells, but the response has been characterized only in the context of a limited number of HLA molecules due to incomplete epitope mapping. We have now greatly expanded the number of defined CD8+T cell epitopes from BZLF1, allowing the response to be evaluated in a much larger proportion of the population. Some regions of the antigen fail to be recognized by CD8+T cells, while others include clusters of overlapping epitopes presented by different HLA molecules. These highly immunogenic regions of BZLF1 include polymorphic sequences, such that up to four overlapping epitopes are impacted by a single amino acid variation common in different regions of the world. This focusing of the immune response to limited regions of the viral protein could be due to sequence similarity to human proteins creating “immune blind spots” through self-tolerance. This study significantly enhances the understanding of the immune response to BZLF1, and the precisely mapped T cell epitopes may be directly exploited in vaccine development and adoptive immunotherapy.IMPORTANCEEpstein-Barr virus (EBV) is an important human pathogen, associated with several malignancies, including nasopharyngeal carcinoma and Hodgkin lymphoma. T lymphocytes are critical for virus control, and clinical trials aimed at manipulating this arm of the immune system have demonstrated efficacy in treating these EBV-associated diseases. These trials have utilized information on the precise location of viral epitopes for T cell recognition, for either measuring or enhancing responses. In this study, we have characterized the T cell response to the highly immunogenic BZLF1 antigen of EBV by greatly expanding the number of defined T cell epitopes. An unusual clustering of epitopes was identified, highlighting a small region of BZLF1 that is targeted by the immune response of a high proportion of the world's population. This focusing of the immune response could be utilized in developing vaccines/therapies with wide coverage, or it could potentially be exploited by the virus to escape the immune response.

scholarly journals Primary Epstein-Barr virus infection does not erode preexisting CD8+ T cell memory in humans

2012 ◽  
Vol 209 (3) ◽  
pp. 471-478 ◽  
Author(s):  
Oludare A. Odumade ◽  
Jennifer A. Knight ◽  
David O. Schmeling ◽  
David Masopust ◽  
Henry H. Balfour ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Epstein Barr Virus ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Acute Epstein-Barr virus (EBV) infection results in an unusually robust CD8+ T cell response in young adults. Based on mouse studies, such a response would be predicted to result in attrition of preexisting memory to heterologous infections like influenza A (Flu) and cytomegalovirus (CMV). Furthermore, many studies have attempted to define the lymphocytosis that occurs during acute EBV infection in humans, but it is unclear whether bystander T cells contribute to it. To address these issues, we performed a longitudinal prospective study of primary EBV infection in humans. During acute EBV infection, both preexisting CMV- and Flu-specific memory CD8+ T cells showed signs of bystander activation, including up-regulation of granzyme B. However, they generally did not expand, suggesting that the profound CD8+ lymphocytosis associated with acute EBV infection is composed largely of EBV-specific T cells. Importantly, the numbers of CMV- and Flu-specific T cells were comparable before and after acute EBV infection. The data support the concept that, in humans, a robust CD8+ T cell response creates a new memory CD8+ T cell niche without substantially depleting preexisting memory for heterologous infections.

scholarly journals Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies

2009 ◽  
Vol 11 (3) ◽  
pp. R77 ◽  
Author(s):  
Corinne Miceli-Richard ◽  
Nicolas Gestermann ◽  
Corinne Amiel ◽  
Jérémie Sellam ◽  
Marc Ittah ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Viral Load ◽  
T Cell ◽  
Cell Response ◽  
Epstein Barr Virus ◽  
T Cell Response ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Cytolytic T-cell response against Epstein-Barr virus in lung cancer patients and healthy subjects

2010 ◽  
Vol 29 (1) ◽  
Author(s):  
Vaios Karanikas ◽  
Maria Zamanakou ◽  
Faye Soukou ◽  
Theodora Kerenidi ◽  
Ioannis Tsougos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Patients ◽  
Cell Response ◽  
Healthy Subjects ◽  
Epstein Barr Virus ◽  
T Cell Response ◽  
Lung Cancer Patients ◽  
Barr Virus ◽  
Epstein Barr

EPSTEIN-BARR VIRUS-SPECIFIC CYTOTOXIC T CELL RESPONSE IN CARDIAC TRANSPLANT RECIPIENTS

1994 ◽  
Vol 57 (11) ◽  
pp. 1611-1616
Author(s):  
Myat T. Kyaw-Tanner ◽  
Donald Esmore ◽  
Scott R. Burrows ◽  
Elizabeth M. Benson ◽  
Tom B. Sculley
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Epstein Barr Virus ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Cardiac Transplant ◽  
Transplant Recipients ◽  
Barr Virus ◽  
Epstein Barr

Rapid reconstitution of Epstein-Barr virus–specific T lymphocytes following allogeneic stem cell transplantation

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2814-2821 ◽  
Author(s):  
Natalie A. Marshall ◽  
John Greg Howe ◽  
Richard Formica ◽  
Diane Krause ◽  
John E. Wagner ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cd8 T Cells ◽  
Epstein Barr Virus ◽  
Hla Class I ◽  
Barr Virus ◽  
Matched Sibling ◽  
Epstein Barr

Epstein-Barr virus (EBV)–specific CD8 T lymphocytes are present at remarkably high frequencies in healthy EBV+individuals and provide protection from EBV-associated lymphoproliferative diseases. Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a commonly used therapy in which T-cell surveillance for EBV is temporarily disrupted. Herein, human leukocyte antigen (HLA) class I tetramers were used to investigate the reestablishment of the EBV-specific CD8 T-cell repertoire in patients following allo-PBSCT. CD8+ T cells specific for lytic and latent cycle–derived EBV peptides rapidly repopulate the periphery of matched sibling allo-PBSCT patients. The relative frequencies of T cells specific for different EBV peptides in transplantation recipients closely reflect those of their respective donors. Investigation of patients at monthly intervals following unmanipulated allo-PBSCT demonstrated that the frequency of EBV-specific T cells correlates with the number of EBV genome copies in the peripheral blood and that expansion of EBV-specific T-cell populations occurs even in the setting of immunosuppressive therapy. In contrast, patients undergoing T-cell–depleted or unrelated cord blood transplantation have undetectable EBV-specific T cells, even in the presence of Epstein-Barr viremia. The protective shield provided by EBV-specific CD8 T cells is rapidly established following unmanipulated matched sibling allo-PBSCT and demonstrates that HLA class I tetramers complexed with viral peptides can provide direct and rapid assessment of pathogen-specific immunity in this and other vulnerable patient populations.

Immunodominant CD8 T cell response to Epstein-Barr virus

2001 ◽  
Vol 55 (7) ◽  
pp. 373-380 ◽  
Author(s):  
E Houssaint ◽  
X Saulquin ◽  
E Scotet ◽  
M Bonneville
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Epstein Barr Virus ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Barr Virus ◽  
Epstein Barr

Oligopeptide Induction of a Secondary Cytotoxic T-cell Response to Epstein-Barr Virus In Vitro

1991 ◽  
Vol 33 (4) ◽  
pp. 411-420 ◽  
Author(s):  
C. SCHMIDT ◽  
S. R. BURROWS ◽  
D. J. MOSS ◽  
T. B. SCULLEY ◽  
I. S. MISKO
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Epstein Barr Virus ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Barr Virus ◽  
Epstein Barr
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