scholarly journals Effect of structural stability on endolysosomal degradation and T-cell reactivity of major shrimp allergen tropomyosin

2020 ◽  
Author(s):  
Sandip D. Kamath ◽  
Sandra Scheiblhofer ◽  
Christopher M. Johnson ◽  
Yoan Machado ◽  
Thomas McLean ◽  
...  
Keyword(s):  
T Cell ◽  
Structural Stability ◽  
Cross Reactivity ◽  
T Cell Epitopes ◽  
Cell Reactivity ◽  
Cell Clones ◽  
T Cell Reactivity ◽  
Minor Allergens ◽  
High Degree ◽  
Shrimp Allergen

AbstractBackgroundTropomyosins are highly conserved proteins, an attribute that forms the molecular basis for their IgE antibody cross-reactivity. Despite structural similarities, their allergenicity varies greatly between ingested and inhaled invertebrate sources. In this study, we investigated the relationship between the structural stability of different tropomyosins, their endolysosomal degradation patterns and T-cell reactivity.MethodsWe investigated the differences between four tropomyosins - the major shrimp allergen Pen m 1 and the minor allergens Der p 10 (dust mite), Bla g 7 (cockroach) and Ani s 3 (fish parasite) - in terms of IgE binding, structural stability, endolysosomal degradation and subsequent peptide generation, and T-cell cross-reactivity in a BALB/c murine model.ResultsDespite their conserved primary structure and consequent IgE co-reactivity, the invertebrate tropomyosins displayed different protein stabilities. Pen m 1 and Ani s 3, but not Der p 10 and Bla g 7 elicited differential melting temperatures that were pH-dependent. Endolysosomal experiments demonstrated differential degradation, as a function of stability, generating different peptide repertoires. Pen m 1 T-cell clones, with specificity for sequences highly conserved in all four tropomyosins, did not proliferate with Der p 10, Bla g 7 and Ani s 3, indicating that these peptides were not naturally produced for other invertebrate tropomyosins.ConclusionsOur data suggest that, although invertebrate tropomyosins exhibit a high degree of IgE cross-reactivity due to conserved B-cell epitopes, they do not necessarily share identical cross-reactive T-cell epitopes. This is likely due to differential endolysosomal processing as a function of different structural stabilities.

scholarly journals Effect of structural stability on endolysosomal degradation and T‐cell reactivity of major shrimp allergen tropomyosin

Allergy ◽  
2020 ◽  
Vol 75 (11) ◽  
pp. 2909-2919 ◽  
Author(s):  
Sandip D. Kamath ◽  
Sandra Scheiblhofer ◽  
Christopher M. Johnson ◽  
Yoan Machado ◽  
Thomas McLean ◽  
...  
Keyword(s):  
T Cell ◽  
Structural Stability ◽  
Cell Reactivity ◽  
T Cell Reactivity ◽  
Shrimp Allergen

scholarly journals Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees.

2021 ◽  
Author(s):  
Alison Tarke ◽  
John Sidney ◽  
Nils Methot ◽  
Yun Zhang ◽  
Jennifer M Dan ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Comprehensive Analysis ◽  
T Cell Epitopes ◽  
Cell Reactivity ◽  
Cell Responses ◽  
Adaptive Immune ◽  
T Cell Reactivity

The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.

scholarly journals BCG Vaccine Derived Peptides Induce SARS-CoV-2 T Cell Cross-Reactivity

2021 ◽  
Vol 12 ◽  
Author(s):  
Peter J. Eggenhuizen ◽  
Boaz H. Ng ◽  
Janet Chang ◽  
Ashleigh L. Fell ◽  
Rachel M. Y. Cheong ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Epidemiological Studies ◽  
Cross Reactivity ◽  
Bcg Vaccine ◽  
Protective Effects ◽  
Cell Reactivity ◽  
Bcg Vaccination ◽  
T Cell Reactivity

Epidemiological studies and clinical trials suggest Bacillus Calmette-Guérin (BCG) vaccine has protective effects against coronavirus disease 2019 (COVID-19). There are now over 30 clinical trials evaluating if BCG vaccination can prevent or reduce the severity of COVID-19. However, the mechanism by which BCG vaccination can induce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses is unknown. Here, we identify 8 novel BCG-derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13-derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG-derived peptide developed enhanced reactivity to its corresponding homologous SARS-CoV-2-derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG-derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG-derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2-derived peptides. These findings provide an in vitro mechanism that may account, in part, for the epidemiologic observation that BCG vaccination confers some protection from COVID-19.

scholarly journals Differential T cell reactivity to seasonal coronaviruses and SARS-CoV-2 in community and health care workers

2021 ◽  
Author(s):  
Ricardo da Silva Antunes ◽  
Suresh Pallikkuth ◽  
Erin Williams ◽  
Esther Dawen Yu ◽  
Jose Mateus ◽  
...  
Keyword(s):  
Health Care ◽  
T Cell ◽  
Health Care Workers ◽  
Cross Reactivity ◽  
Cell Reactivity ◽  
Cell Responses ◽  
Care Workers ◽  
Community Controls ◽  
T Cell Reactivity

AbstractHerein we measured CD4+ T cell responses against common cold corona (CCC) viruses and SARS-CoV-2 in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC reactive T cells in SARS-CoV-2 seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC reactivity was decreased in SARS-CoV-2 infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego.

scholarly journals Proteins of the Rpf Family: Immune Cell Reactivity and Vaccination Efficacy against Tuberculosis in Mice

2003 ◽  
Vol 71 (8) ◽  
pp. 4789-4794 ◽  
Author(s):  
Vladimir V. Yeremeev ◽  
Tatiana K. Kondratieva ◽  
Elvira I. Rubakova ◽  
Svetlana N. Petrovskaya ◽  
Konstantin A. Kazarian ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Cell ◽  
Micrococcus Luteus ◽  
Interleukin 10 ◽  
Cross Reactivity ◽  
High Dose ◽  
Host Immune System ◽  
Survival Times ◽  
Cell Reactivity ◽  
High Degree

ABSTRACT It was shown recently that Mycobacterium tuberculosis expresses five proteins that are homologous to Rpf (resuscitation promoting factor), which is secreted by growing cells of Micrococcus luteus. Rpf is required to resuscitate the growth of dormant Micrococcus luteus organisms, and its homologues may be involved in mycobacterial reactivation. Mycobacterial Rpf-like products are secreted proteins, which makes them candidates for recognition by the host immune system and anti-Rpf immune responses potentially protective against reactivated tuberculosis. Here we report that the Rpf protein itself and four out of five of its mycobacterial homologues, which were administered as subunit vaccines to C57BL/6 mice, are highly immunogenic. Rpf-like proteins elicit immunoglobulin G1 (IgG1) and IgG2a responses and T-cell proliferation and stimulate production of gamma interferon, interleukin-10 (IL-10), and IL-12 but not IL-4 or IL-5. Both humoral and T-cell responses against these antigens show a high degree of cross-reactivity. Vaccination of mice with Rpf-like proteins results in a significant level of protection against a subsequent high-dose challenge with virulent M. tuberculosis H37Rv, both in terms of survival times and mycobacterial multiplication in lungs and spleens.

scholarly journals T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

2001 ◽  
Vol 69 (9) ◽  
pp. 5345-5351 ◽  
Author(s):  
Luiza Guilherme ◽  
Sandra E. Oshiro ◽  
Kellen C. Faé ◽  
Edécio Cunha-Neto ◽  
Guilherme Renesto ◽  
...  
Keyword(s):  
T Cells ◽  
Heart Disease ◽  
T Cell ◽  
Rheumatic Heart Disease ◽  
Peripheral Blood ◽  
Cell Reactivity ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Reactivity ◽  
Rheumatic Heart

ABSTRACT T-cell molecular mimicry between streptococcal and heart proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). We searched for immunodominant T-cell M5 epitopes among RHD patients with defined clinical outcomes and compared the T-cell reactivities of peripheral blood and intralesional T cells from patients with severe RHD. The role of HLA class II molecules in the presentation of M5 peptides was also evaluated. We studied the T-cell reactivity against M5 peptides and heart proteins on peripheral blood mononuclear cells (PBMC) from 74 RHD patients grouped according to the severity of disease, along with intralesional and peripheral T-cell clones from RHD patients. Peptides encompassing residues 1 to 25, 81 to 103, 125 to 139, and 163 to 177 were more frequently recognized by PBMC from RHD patients than by those from controls. The M5 peptide encompassing residues 81 to 96 [M5(81–96) peptide] was most frequently recognized by PBMC from HLA-DR7+DR53+ patients with severe RHD, and 46.9% (15 of 32) and 43% (3 of 7) of heart-infiltrating and PBMC-derived peptide-reactive T-cell clones, respectively, recognized the M5(81–103) region. Heart proteins were recognized more frequently by PBMC from patients with severe RHD than by those from patients with mild RHD. The similar pattern of T-cell reactivity found with both peripheral blood and heart-infiltrating T cells is consistent with the migration of M-protein-sensitized T cells to the heart tissue. Conversely, the presence of heart-reactive T cells in the PBMC of patients with severe RHD also suggests a spillover of sensitized T cells from the heart lesion.

scholarly journals Differential T cell reactivity to endemic coronaviruses and SARS-CoV-2 in community and health care workers

2021 ◽  
Author(s):  
Ricardo da Silva Antunes ◽  
Suresh Pallikkuth ◽  
Erin Williams ◽  
Dawen Yu Esther ◽  
Jose Mateus ◽  
...  
Keyword(s):  
Health Care ◽  
T Cell ◽  
Health Care Workers ◽  
Cross Reactivity ◽  
Cell Reactivity ◽  
Cell Responses ◽  
Care Workers ◽  
Community Controls ◽  
T Cell Reactivity

Abstract Herein we measured CD4 + T cell responses against common cold corona (CCC) viruses and SARS-CoV-2 in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC reactive T cells in SARS-CoV-2 seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T cell reactivity was decreased in SARS-CoV-2 infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego.

scholarly journals Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Swapnil Mahajan ◽  
Vasumathi Kode ◽  
Keshav Bhojak ◽  
Coral Karunakaran ◽  
Kayla Lee ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
T Cell Epitopes ◽  
Cell Reactivity ◽  
Cell Immunity ◽  
T Cell Reactivity ◽  
Shared Epitopes

AbstractThe COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spike antigen using a novel TCR-binding algorithm. The predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. The T-cell reactivity to the predicted epitopes was higher than the Spike-S1 and S2 peptide pools in the unexposed donors. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. This finding is in contrast to multiple published studies in which pre-existing T-cell immunity is suggested to arise from shared epitopes between SARS-CoV-2 and other common cold-causing coronaviruses. However, our findings suggest that SARS-CoV-2 reactive T-cells are likely to be present in many individuals because of prior exposure to flu and CMV viruses.

Elimination of a Human T-cell Region in Staphylokinase by T-cell Screening and Computer Modeling

2002 ◽  
Vol 87 (04) ◽  
pp. 666-673 ◽  
Author(s):  
Stéphane Plaisance ◽  
Kristel Vanderlick ◽  
Petra Vandervoort ◽  
Kathleen Brepoels ◽  
Désiré Collen ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
T Cell ◽  
Computer Modeling ◽  
T Cell Epitopes ◽  
Cell Reactivity ◽  
T Cell Clones ◽  
Human T Cell ◽  
Hla Dr ◽  
Cell Clones

SummaryStaphylokinase is a potent highly fibrin-selective thrombolytic agent, but it induces a humoral immune response in most treated patients. Staphylokinase-specific T-lymphocytes can be found in normal healthy individuals, from whom a large panel of staphylokinasespecific T-cells were cloned. The staphylokinase amino acid sequence 71-87 was widely recognized, as it induced proliferation of T-cell clones isolated from 90% of the donors. Computer modeling of this area, threaded as 11-mer peptides within the peptide-binding groove of the major HLA-DR alleles, indicated two putative partially overlapping binding sequences. The region-(71-87)-specific T-cell clones recognized either one or the other minimal peptide, confirming that both sequences could be functional T-cell epitopes. Furthermore, to guide the mutagenesis to eliminate T-cell reactivity, the contribution of each residue to the HLA-DR-anchoring and T-cell receptor exposure was evaluated for both binding motifs. Computer calculations combined with functional assays resulted in the design of staphylokinasevariants, including 2 to 4 amino acid substitutions in the region 71-87. These variants were no longer recognized by the region-(71-87)specific T-cell clones, and importantly no new staphylokinase-variantspecific cellular immune response could be measured.

scholarly journals Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2

Science ◽  
2021 ◽  
pp. eabg8985
Author(s):  
Jun Siong Low ◽  
Daniela Vaqueirinho ◽  
Federico Mele ◽  
Mathilde Foglierini ◽  
Josipa Jerak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cross Reactivity ◽  
T Cell Response ◽  
T Cell Epitopes ◽  
Subunit Vaccines ◽  
Hla Dr ◽  
Cell Clones ◽  
Nucleoprotein N

The identification of CD4+ T cell epitopes is instrumental for the design of subunit vaccines for broad protection against coronaviruses. Here we demonstrate in COVID-19-recovered individuals a robust CD4+ T cell response to naturally processed SARS-CoV-2 spike (S) and nucleoprotein (N), including effector, helper, and memory T cells. By characterizing 2943 S-reactive T cell clones from 34 individuals, we found that 34% of clones and 93% of individuals recognized a conserved immunodominant S346-365 region within the RBD comprising nested HLA-DR- and HLA-DP-restricted epitopes. Using pre- and post-COVID-19 samples and S proteins from endemic coronaviruses, we identify cross-reactive T cells targeting multiple S protein sites. The immunodominant and cross-reactive epitopes identified can inform vaccination strategies to counteract emerging SARS-CoV-2 variants.

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