scholarly journals Repertoire of HLA-DR1-Restricted CD4 T-Cell Responses to Capsular Caf1 Antigen of Yersinia pestis in Human Leukocyte Antigen Transgenic Mice

2010 ◽  
Vol 78 (10) ◽  
pp. 4356-4362 ◽  
Author(s):  
Julie A. Musson ◽  
Rebecca Ingram ◽  
Guillaume Durand ◽  
Stephanie Ascough ◽  
Emma L. Waters ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Yersinia Pestis ◽  
Direct Determination ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Immunodominant Epitope ◽  
Cell Responses ◽  
Human T Cell ◽  
Cell Immunity

ABSTRACT Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under development as a recombinant vaccine. However, little is known about the specificity of human T-cell responses for Caf1. We characterized CD4 T-cell epitopes of Caf1 in “humanized” HLA-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T-cell immunity was measured with respect to proliferative and gamma interferon T-cell responses and recognition by a panel of T-cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased toward a single immunodominant epitope near the C terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.

scholarly journals A novel polyepitope vaccine elicited HIV peptide specific CD4+ T cell responses in HLA-A2/DRB1 transgenic mice

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0184207 ◽  
Author(s):  
Haitao Liu ◽  
Wei Shen ◽  
Jiayi Shu ◽  
Zhihua Kou ◽  
Xia Jin
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals Differential CD4+T-cell responses of allergic and non-allergic subjects to the immunodominant epitope region of the horse major allergenEqu c 1

Immunology ◽  
2013 ◽  
Vol 141 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Anssi Kailaanmäki ◽  
Tuure Kinnunen ◽  
William W. Kwok ◽  
Marja Rytkönen-Nissinen ◽  
Jukka Randell ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Immunodominant Epitope ◽  
Epitope Region ◽  
Cell Responses

scholarly journals Metal-specific CD4+ T-cell responses induced by beryllium exposure in HLA-DP2 transgenic mice

2015 ◽  
Vol 9 (1) ◽  
pp. 218-228 ◽  
Author(s):  
M T Falta ◽  
A N Tinega ◽  
D G Mack ◽  
N A Bowerman ◽  
F Crawford ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals Enteropathy-induced regulatory T cells inhibit intestinal CD4+ T cell responses against oral vaccines

2020 ◽  
Author(s):  
Amrita Bhattacharjee ◽  
Ansen H.P. Burr ◽  
Abigail E. Overacre-Delgoffe ◽  
Justin T. Tometich ◽  
Deyi Yang ◽  
...  
Keyword(s):  
Small Intestine ◽  
T Cell ◽  
Intestinal Inflammation ◽  
Oral Vaccine ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Oral Vaccines ◽  
Vaccine Response ◽  
Cell Responses ◽  
Cell Immunity

SummaryEnvironmental Enteric Dysfunction (EED) is an intestinal disease caused by malnutrition and infection that leads to malabsorption and stunting. EED is also associated with a reduced efficacy of oral vaccines. We show in a microbiota and diet-dependent model of EED that oral vaccine-specific CD4+ T cell responses fail in the small intestine but responses in the draining lymph node were unaffected. Accordingly, the number of immunosuppressive RORγT+FOXP3+ Tregs in the small intestine inversely correlated with the response to oral vaccination. Depletion of RORγT+FOXP3+ Tregs indicated that they were necessary for EED-associated inhibition of the vaccine response. Additionally, RORγT+FOXP3+ Tregs are important to regulate EED-associated inflammation as their depletion significantly worsened stunting. We have shown that EED-associated intestinal inflammation leads to a localized intestinal blockade of CD4 T cell immunity. These results support a modular model for immunity where tissue responses can be regulated independently of systemic immunity to prevent autoinflammation.

scholarly journals Quantitation of CD8+ T Cell Responses to Newly Identified HLA-A*0201–restricted T Cell Epitopes Conserved Among Vaccinia and Variola (Smallpox) Viruses

2003 ◽  
Vol 197 (7) ◽  
pp. 927-932 ◽  
Author(s):  
Masanori Terajima ◽  
John Cruz ◽  
Gregory Raines ◽  
Elizabeth D. Kilpatrick ◽  
Jeffrey S. Kennedy ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Epitopes ◽  
Primary Immunization ◽  
Cell Responses ◽  
Human T Cell ◽  
Cell Immunity ◽  
Ifn Γ

Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia, suggesting the importance of T cell immunity in recovery from infection. In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201. Both epitopes are highly conserved in vaccinia and variola viruses. The frequency of vaccinia-specific CD8+ T cell responses to these epitopes measured by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay and HLA/peptide tetramer staining peaked 2 wk after primary immunization and then declined, but were still detectable 1 to 3 yr after primary immunization. 2 wk after immunization, IFN-γ–producing cells specific to these two epitopes were 14% of total vaccinia virus-specific IFN-γ–producing cells in one donor, 35% in the second donor, and 6% in the third donor. This information will be useful for studies of human T cell memory and for the design and analyses of the immunogenicity of experimental vaccinia vaccines.

scholarly journals Factors influencing maternal microchimerism throughout infancy and its impact on infant T cell immunity

2021 ◽  
Author(s):  
Christina Balle ◽  
Agano Kiravu ◽  
Angela Hoffmann ◽  
Anna-Ursula Happel ◽  
Sami B. Kanaan ◽  
...  
Keyword(s):  
T Cell ◽  
Whole Blood ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Cell Immunity ◽  
Hiv Exposed ◽  
The Impact ◽  
Exposed Uninfected

AbstractDeterminants of the acqusition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors which influence MMc detection and level across infancy and the effect of MMc on T cell responses to BCG vaccination in a cohort of HIV exposed, uninfected and HIV unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day one and 7, 15, and 36 weeks of life. Infants received BCG at birth, and select whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional CD4+ T cell responses. MMc was present in most infants across infancy at levels ranging from 1-1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, exclusive breastfeeding, and female sex, emphasizing that both maternal and infant factors may shape the maternal graft. Initiation of maternal antiretroviral therapy prior to pregnancy was associated with partial restoration of MMc in HIV exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional CD4+ T cell response to BCG, suggesting that MMc may functionally impact infant immunity.

scholarly journals SARS-CoV-2-specific T cell memory is long-lasting in the majority of convalsecent COVID-19 individuals

2020 ◽  
Author(s):  
Ziwei Li ◽  
Jing Liu ◽  
Hui Deng ◽  
Xuecheng Yang ◽  
Hua Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Onset ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Long Term Memory ◽  
Memory T Cell ◽  
Cell Responses ◽  
Cell Immunity

ABSTRACTAn unaddressed key question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of immunity for which specific T cell responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an indispensable element. Being situated in Wuhan where the pandemic initiated enables us to conduct the longest analyses of memory T cell responses against SARS-CoV-2 in COVID-19 convalescent individuals (CIs). Magnitude and breadth of SARS-CoV-2 memory CD4 and CD8 T cell responses were heterogeneous between patients but robust responses could be detected up to 9 months post disease onset in most CIs. Loss of memory CD4 and CD8 T cell responses were observed in only 16.13% and 25.81% of CIs, respectively. Thus, the overall magnitude and breadth of memory CD4 and CD8 T cell responses were quite stable and not inversely correlated with the time from disease onset. Interestingly, the only significant decrease in the response was found for memory CD4 T cells in the first 6-month post COVID-19 disease onset. Longitudinal analyses revealed that the kinetics of SARS-CoV-2 memory CD4 and CD8 T cell responses were quite heterogenous between patients. Loss of memory CD4 T cell responses was observed more frequently in asymptomatic cases than after symptomatic COVID-19. Interestingly, the few CIs in which SARS-CoV-2-specific IgG responses disappeared showed more durable memory CD4 T cell responses than CIs who remained IgG-positive for month. Collectively, we provide the first comprehensive characterization of the long-term memory T cell response in CIs, suggesting that SARS-CoV-2-specific T cell immunity is long-lasting in the majority of individuals.

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