T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity

ABSTRACTAlthough parasite strain-restricted CD8 T cell responses have been described for several protozoa, the precise role of antigenic variability in immunity is poorly understood. The tick-borne protozoan parasiteTheileria annulatainfects leukocytes and causes an acute, often fatal lymphoproliferative disease in cattle. Building on previous evidence of strain-restricted CD8 T cell responses toT. annulata, this study set out to identify and characterize the variability of the target antigens. Three antigens were identified by screening expressed parasite cDNAs with specific CD8 T cell lines. In cattle expressing the A10 class I major histocompatibility complex haplotype, A10-restricted CD8 T cell responses were shown to be focused entirely on a single dominant epitope in one of these antigens (Ta9). Sequencing of the Ta9 gene from field isolates ofT. annulatademonstrated extensive sequence divergence, resulting in amino acid polymorphism within the A10-restricted epitope and a second A14-restricted epitope. Statistical analysis of the allelic sequences revealed evidence of positive selection for amino acid substitutions within the region encoding the CD8 T cell epitopes. Sequence differences in the A10-restricted epitope were shown to result in differential recognition by individual CD8 T cell clones, while clones also differed in their ability to recognize different alleles. Moreover, the representation of these clonal specificities within the responding CD8 T cell populations differed between animals. As well as providing an explanation for incomplete protection observed after heterologous parasite challenge of vaccinated cattle, these results have important implications for the choice of antigens for the development of novel subunit vaccines.

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COVID-19 patients display distinct SARS-CoV-2 specific T-cell responses according to disease severity

Journal of Infection ◽

10.1016/j.jinf.2020.08.036 ◽

2020 ◽

pp. 4816 ◽

Cited By ~ 7

Author(s):

Marie Kroemer ◽

Laurie Spehner ◽

Lucie Vettoretti ◽

Adeline Bouard ◽

Guillaume Eberst ◽

...

Keyword(s):

T Cell ◽

Disease Severity ◽

T Cell Responses ◽

Cell Responses

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HLA-restricted epitope identification and detection of functional T cell responses by using MHC-peptide and costimulatory microarrays

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0407019102 ◽

2005 ◽

Vol 102 (10) ◽

pp. 3744-3749 ◽

Cited By ~ 58

Author(s):

J. D. Stone ◽

W. E. Demkowicz ◽

L. J. Stern

Keyword(s):

T Cell ◽

T Cell Responses ◽

Cell Responses ◽

Epitope Identification ◽

Restricted Epitope

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Altered decamer and nonamer from an HLA-A0201-restricted epitope of Survivin differentially stimulate T-cell responses in different individuals

Vaccine ◽

10.1016/j.vaccine.2011.01.115 ◽

2011 ◽

Vol 29 (16) ◽

pp. 3021-3030 ◽

Cited By ~ 10

Author(s):

Chantale Bernatchez ◽

Kuichin Zhu ◽

Yufeng Li ◽

Helen Andersson ◽

Constantin Ionnides ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Cell Responses ◽

Restricted Epitope

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Celiac Disease Association with CD8+ T Cell Responses: Identification of a Novel Gliadin-Derived HLA-A2-Restricted Epitope

The Journal of Immunology ◽

10.4049/jimmunol.170.5.2719 ◽

2003 ◽

Vol 170 (5) ◽

pp. 2719-2726 ◽

Cited By ~ 59

Author(s):

Carmen Gianfrani ◽

Riccardo Troncone ◽

Patrizia Mugione ◽

Elena Cosentini ◽

Mariateresa De Pascale ◽

...

Keyword(s):

Celiac Disease ◽

T Cell ◽

T Cell Responses ◽

Cd8 T Cell ◽

Disease Association ◽

Cell Responses ◽

Restricted Epitope

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Quantification of dengue virus specific T cell responses and correlation with viral load and clinical disease severity in acute dengue infection

10.1101/325944 ◽

2018 ◽

Author(s):

Dulharie T. Wijeratne ◽

Samitha Fernando ◽

Laksiri Gomes ◽

Chandima Jeewandara ◽

Anushka Ginneliya ◽

...

Keyword(s):

T Cell ◽

Dengue Virus ◽

Disease Severity ◽

Ex Vivo ◽

Dengue Infection ◽

T Cell Responses ◽

Clinical Disease ◽

Cell Responses ◽

Early Appearance ◽

Liver Transaminases

AbstractBackgroundIn order to understand the role of dengue virus (DENV) specific T cell responses that associate with protection, we studied their frequency and phenotype in relation to clinical disease severity and resolution of viraemia in a large cohort of patients with varying severity of acute dengue infection.Methodology/Principal findingsUsing ex vivo IFNγ ELISpot assays we determined the frequency of dengue viral peptide (DENV)-NS3, NS1 and NS5 responsive T cells in 74 adult patients with acute dengue infection and examined the association of responsive T cell frequency with the extent of viraemia and clinical disease severity. We found that total DENV-specific and DENV-NS3-specific T cell responses, were higher in patients with dengue fever (DF), when compared to those with dengue haemorrhagic fever (DHF). In addition, early appearance of DENV-specific T cell responses was significantly associated with milder clinical disease (p=0.02). DENV peptide specific T cell responses inversely correlated with the degree of viraemia, which was most significant for DENV-NS3 specific T cell responses (Spearman’s r = −0.47, p=0.0003). The frequency of T cell responses to NS1, NS5 and pooled DENV peptides, correlated with the degree of thrombocytopenia but had no association with levels of liver transaminases. In contrast, DENV-IgG inversely correlated with the degree of thrombocytopenia and levels of liver transaminases.Conclusions/significanceEarly appearance of DENV-specific T cell IFNγ responses appears to associate with milder clinical disease and resolution of viraemia, suggesting a protective role in acute dengue infection.

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Differential regulation of T cell responses and disease severity by mycoplasma and its superantigen in autoimmune diabetic mice

Frontiers in Immunology ◽

10.3389/conf.fimmu.2013.02.00091 ◽

2013 ◽

Vol 4 ◽

Author(s):

Nourian Maziar ◽

Mu Hong

Keyword(s):

T Cell ◽

Disease Severity ◽

T Cell Responses ◽

Differential Regulation ◽

Diabetic Mice ◽

Cell Responses

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SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

10.1101/2020.10.08.331645 ◽

2020 ◽

Author(s):

Stine SF Nielsen ◽

Line K Vibholm ◽

Ida Monrad ◽

Rikke Olesen ◽

Giacomo S Frattari ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Immune Responses ◽

Disease Severity ◽

Adaptive Immune Response ◽

T Cell Responses ◽

Adaptive Immune Responses ◽

Cell Responses ◽

Adaptive Immune ◽

Robust Adaptive

AbstractThe SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search for treatments and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. We investigated the breadth and potency of antibody-, and T-cell immune responses, in 203 recovered SARS-CoV-2 infected patients who presented with asymptomatic to severe infections. We report very broad serological profiles with cross-reactivity to other human coronaviruses. Further, >99% had SARS-CoV-2 epitope specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 95% of individuals. A significant positive correlation between spike-ACE2 blocking antibody titers and neutralization potency was observed. SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 90% of HLA-A2+ individuals. The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of disease severity.Author summarySARS-CoV-2 can cause severe and deadly infections. However, the immunological understanding of this viral infection is limited. Currently, several vaccines are being developed to help limit transmission and prevent the current pandemic. However, basic understanding of the adaptive immune response developed during SARS-CoV-2 infections is needed to inform further vaccine development and to understand the protective properties of the developed immune response. We investigated, the adaptive immune response developed during SARS-CoV-2 infections in recovered patients experiencing a full spectrum of disease severity, from asymptomatic infections to severe cases requiring hospitalization. We used a novel multiplex serological platform, cell-based neutralization assays and dextramer flow cytometry assays to characterize a broad and robust humoral and cellular immune response towards SARS-CoV-2. We found that the vast majority of recovered individuals have clear detectable and functional SARS-CoV-2 spike specific adaptive immune responses, despite diverse disease severities. The detection of both a humoral and cellular functional spike specific immune response in the vast majority of the individuals, irrespective of asymptomatic manifestations, supports vaccine designs currently underway, and encourages further exploration of whether primary infections provide protection to reinfection.

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