scholarly journals Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens

Author(s):  
Yoya Vashi ◽  
Vipin Jagrit ◽  
Sachin Kumar

AbstractThe 2019 novel severe respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide. The present study followed computational approaches to identify B- and T-cell epitopes for spike glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified twenty-four peptide stretches on the SARS-CoV-2 spike protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface. Out of which twenty are surface exposed and predicted to have reasonable epitope binding efficiency. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics.

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2227-2236 ◽  
Author(s):  
NA Kernan ◽  
C Bordignon ◽  
G Heller ◽  
I Cunningham ◽  
H Castro-Malaspina ◽  
...  

Abstract Risk factors for graft failure were analyzed in 122 recipients of an allogeneic T-cell-depleted human leukocyte antigen (HLA)-identical sibling marrow transplant as treatment for leukemia. In each case pretransplant immunosuppression included 1,375 to 1,500 cGy hyperfractionated total body irradiation and cyclophosphamide (60 mg/kg/d x 2). No patient received immunosuppression prosttransplant for graft-versus-host disease (GVHD) prophylaxis. Nineteen patients in this group experienced graft failure. The major factors associated with graft failure were transplants from male donors and the age of the patient (or donor). Among male recipients of male donor-derived grafts a low dose per kilogram of nucleated cells, progenitor cells (colony forming unit-GM) and T cells was also associated with graft failure. Additional irradiation to 1,500 cGy, high dose corticosteroids posttransplant, and additional peripheral blood donor T cells did not decrease the incidence of graft failure. In addition, type of leukemia, time from diagnosis to transplant, an intact spleen, or the presence of antidonor leukocyte antibodies did not correlate with graft failure. To ensure engraftment of secondary transplants, further immunosuppression was necessary but was poorly tolerated. However, engraftment and survival could be achieved with an immunosuppressive regimen in which antithymocyte globulin and high dose methylprednisolone were administered both before and after infusions of secondary partially T- cell-depleted marrow grafts.


Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2352-2357 ◽  
Author(s):  
Alvaro Urbano-Ispizua ◽  
Enric Carreras ◽  
Pedro Marı́n ◽  
Montserrat Rovira ◽  
Carmen Martı́nez ◽  
...  

Clinical results after T-cell–depleted allografts might be improved by modifying the graft content of progenitor and accessory cells. Although the association of the number of donor T cells with the clinical outcome has been studied extensively, the optimum number of progenitor cells that should be administered to patients is unknown. The characteristics of 84 consecutive human leukocyte antigen (HLA)–identical sibling transplants of granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood progenitor cells depleted of T cells by CD34+ positive selection (allo-PBT/CD34+) were analyzed for their effect on clinical outcome. After a median follow-up of 24 months (range, 1-70 months), 50 patients remain alive (59.5%) and 34 have died (21 [25%] as a result of the transplant and 13 [15.5%] due to disease relapse). The median number of CD34+ cells administered to the patients was 3.9 × 106/kg (range, 1.2-14.3 × 106/kg). A number of CD34+ cells in the inoculum of 1 × 106/kg to 3 × 106/kg was associated with increased survival: 21 of 28 (75%) patients are alive, as compared with 29 of 56 (52%) patients receiving more than 3 × 106/kg (actuarial probability 75% vs. 42%, respectively; P = .01). In the multivariate analysis, the independent prognostic variables for survival were CD34+cell dose 1 × 106/kg to 3 × 106/kg (RR = 4.8; P = .0008), sex-pairing match (RR = 3.2;P = .002), and early stage of disease (RR = 2.8;P = .007). From these results it appears that, in allo-PBT/CD34+ from HLA-identical siblings, a number of CD34+ cells in the inoculum between 1 × 106/kg to 3 × 106/kg is an important factor for better survival, and that higher CD34+ cell doses might be associated with a poorer outcome.


Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 788-797 ◽  
Author(s):  
Aaron P. Rapoport ◽  
Nicole A. Aqui ◽  
Edward A. Stadtmauer ◽  
Dan T. Vogl ◽  
Hong-Bin Fang ◽  
...  

AbstractIn a phase 1/2 two-arm trial, 54 patients with myeloma received autografts followed by ex vivo anti-CD3/anti-CD28 costimulated autologous T cells at day 2 after transplantation. Study patients positive for human leukocyte antigen A2 (arm A, n = 28) also received pneumococcal conjugate vaccine immunizations before and after transplantation and a multipeptide tumor antigen vaccine derived from the human telomerase reverse transcriptase and the antiapoptotic protein survivin. Patients negative for human leukocyte antigen A2 (arm B, n = 26) received the pneumococcal conjugate vaccine only. Patients exhibited robust T-cell recoveries by day 14 with supraphysiologic T-cell counts accompanied by a sustained reduction in regulatory T cells. The median event-free survival (EFS) for all patients is 20 months (95% confidence interval, 14.6-24.7 months); the projected 3-year overall survival is 83%. A subset of patients in arm A (36%) developed immune responses to the tumor antigen vaccine by tetramer assays, but this cohort did not exhibit better EFS. Higher posttransplantation CD4+ T-cell counts and a lower percentage of FOXP3+ T cells were associated with improved EFS. Patients exhibited accelerated polyclonal immunoglobulin recovery compared with patients without T-cell transfers. Adoptive transfer of tumor antigen vaccine-primed and costimulated T cells leads to augmented and accelerated cellular and humoral immune reconstitution, including antitumor immunity, after autologous stem cell transplantation for myeloma. This study was registered at www.clinicaltrials.gov as NCT00499577.


1978 ◽  
Vol 147 (1) ◽  
pp. 137-146 ◽  
Author(s):  
E G Engleman ◽  
A J McMichael ◽  
M E Batey ◽  
H O McDevitt

It has previously been shown that J.H., a human leukocyte antigen (HLA)-Dw2 homozygous multiparous woman, fails to respond in a mixed lymphocyte reaction (MLR) to her Dw1 homozygous husband W.H., and that her T cells suppress the responses of HLA matched responders to W.H. The present studies take advantage of the observation that J.H. suppressor cells resist a dose of gamma-irradiation which functionally eliminates her MLR responder cells. J.H. cells, depleted of alloreactive cells, suppress the responses of Dw2 heterozygous or homozygous cells to W.H., regardless of their associated HLA-A or B antigens. Only when W.H. or a few other cells are present as the irradiated stimulator is J.H. suppression of Dw2 responses detected. Thus, the J.H. suppressor T cell recognizes determinants in the irradiated stimulator cells as well as D locus products in the responder.


Hepatology ◽  
2013 ◽  
Vol 57 (2) ◽  
pp. 727-739 ◽  
Author(s):  
Manal M. Monshi ◽  
Lee Faulkner ◽  
Andrew Gibson ◽  
Rosalind E. Jenkins ◽  
John Farrell ◽  
...  

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