MHC II tetramers visualize human CD4+ T cell responses to Epstein–Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response

Long, Heather M.; Chagoury, Odette; Leese, Alison M.; Ryan, Gavin; James, Eddie A.; Morton, Laura T.; Abbott, Rachel J. M.; Sabbah, Shereen; Kwok, William W.; Rickinson, Alan B.

doi:10.1084/jem.20121437

Cited by 92 publications

(120 citation statements)

References 57 publications

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“…38 Although formal proof that such cells represented T SCM lymphocytes was missing in these reports, these findings strongly support the hypothesis that T SCM lymphocytes are reproducibly generated after immunization in humans. Differences in the insulting pathogens and tissue environments might impinge on the relative abundance of T SCM generated.…”

supporting

confidence: 60%

Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation

Cieri

Oliveira

Greco

et al. 2015

Blood

122

128

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Key Points• T SCM lymphocytes are preferentially generated from naive precursors in vivo early after haploidentical HSCT.• T SCM represent relevant novel players in the diversification of immunological memory after haploidentical HSCT.Memory stem T cells (T SCM ) have been proposed as key determinants of immunologic memory. However, their exact contribution to a mounting immune response, as well as the mechanisms and timing of their in vivo generation, are poorly understood. We longitudinally tracked T SCM dynamics in patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), thereby providing novel hints on the contribution of this subset to posttransplant immune reconstitution in humans. We found that donor-derived T SCM are highly enriched early after HSCT. We showed at the antigenspecific and clonal level that T SCM lymphocytes can differentiate directly from naive precursors infused within the graft and that the extent of T SCM generation might correlate with interleukin 7 serum levels. In vivo fate mapping through T-cell receptor sequencing allowed defining the in vivo differentiation landscapes of human naive T cells, supporting the notion that progenies of single naive cells embrace disparate fates in vivo and highlighting T SCM as relevant novel players in the diversification of immunological memory after allogeneic HSCT. (Blood. 2015;125(18):2865-2874

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supporting

confidence: 60%

Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation

Cieri

Oliveira

Greco

et al. 2015

Blood

122

128

View full text Add to dashboard Cite

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“…Antibody to EBNA1 appears later in the sera than antibody to other EBV latency proteins, including EBNA2, EBNA3, and EBNA-LP (5,27). There is a similarly delayed appearance of CD4 T cell responses to EBNA1 in the blood after the onset of IM compared with EBNA2 and other EBV lytic proteins (28). This delay may be due to the fact that, unlike EBV lytic proteins and the other EBNAs, EBNA1 is not normally released from EBV-infected cells or that EBNA1 inhibits its own translation and degradation, resulting in reduced presentation to T cells.…”

Section: Figmentioning

confidence: 95%

Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV

Hayes

Liu

et al. 2016

Clin Vaccine Immunol

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Prospective studies of antibodies to multiple Epstein-Barr virus (EBV) proteins and EBV neutralizing antibodies in the same individuals before, during, and after primary EBV infection have not been reported. We studied antibody responses to EBV in college students who acquired primary EBV infection during prospective surveillance and correlated the kinetics of antibody response with the severity of disease. Neutralizing antibodies and enzyme-linked immunosorbent assay (ELISA) antibodies to gp350, the major target of neutralizing antibody, reached peak levels at medians of 179 and 333 days after the onset of symptoms of infectious mononucleosis, respectively. No clear correlation was found between the severity of the symptoms of infectious mononucleosis and the peak levels of antibody to individual viral proteins or to neutralizing antibody. In summary, we found that titers of neutralizing antibody and antibodies to multiple EBV proteins increase over many months after primary infection with EBV.

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“…30 These results provide solid evidence that AgAbs can reactivate circulating resting EBV-specific memory T cells and strongly increase the probability that this approach will elicit a potent T-cell response in vivo.…”

Section: Agab Can Efficiently Vehicle Large Protein Segments Into B Cmentioning

confidence: 58%

Antigen-armed antibodies targeting B lymphoma cells effectively activate antigen-specific CD4+ T cells

Ilecka

Bartlett

et al. 2015

Blood

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MHC II tetramers visualize human CD4+ T cell responses to Epstein–Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response

Abstract: Characterization of the human EBV-specific CD4+ T cell response using MHC II tetramers reveals the latent EBV antigen response is more frequent than the lytic response with a delayed EBNA1 response that coincides with diminished cross-presentation.

Cited by 92 publications

References 57 publications

Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation

Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation

Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV

Antigen-armed antibodies targeting B lymphoma cells effectively activate antigen-specific CD4+ T cells

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