Exciting findings regarding CD8 T cell response in recovered COVID patients

An international team of scientists have identified a novel T cell recognition epitope across various proteins of severe acute respiratory syndrome coronavirus 2 in patients recovered with COVID-19. Scientists have also characterized the phenotype of the T cell population. Research is currently bioRxiv* Preprint server.

Since its advent in December 2019, more than 37.3 million people have had the fatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Infects and kills more than 1 million people. World wide. Patients with COVID-19 have been observed to have a variety of clinical effects, from asymptomatic or mild infections to severe or life-threatening infections.

Various immune responses to SARS-CoV-2 have been observed, with higher antibody titers being associated with male gender, age, and hospitalization. Many studies have shown that a T-cell immune response to SARS-CoV-2 may provide long-term protection. A strong SARS-CoV-2 specific T cell response has been observed in patients who have recovered with COVID-19. Similarly, a strong CD8 + T cell immune response has been observed in COVID-19 patients with mild symptoms.

Given the important involvement of T cells To alleviate the severity of the disease, it is essential to study the specific targets of T cells in the viral proteome and the clinical effects of T cell-mediated targeting.

Identification and characterization of SARS-CoV-2 specific CD8 + T cells from SARS-CoV-2 convalescent donors. A) Visualization and schematic of the workflow. SARS-CoV2-specific CD8 + T cells were identified by PBMCs from convalescent donors and at the same time totaled 408 across 6 HLA using a mass cytometry-based highly multiplexed tetramer staining approach. Was characterized by screening for SARS-CoV-2 candidate epitopes. SARS-CoV-2 specific T cell frequency and phenotypic profile were associated with and correlated with sample-specific humoral response and cross-section of inflammatory parameters.

Current research purpose

In the current study, scientists aimed to identify CD8 + T cell recognition epitopes in COVID-19 recovery patients across a variety of SARS-CoV-2 proteins. They also evaluated the phenotypic characteristics of these CD8 + T cells.

Important findings

Scientists analyzed 30 Convalescent plasma Samples for identifying and characterizing SARS-CoV-2 specific CD8 + T cell populations using a mass cytometry-based multiple tetramer staining approach (donor age range: 19-77 years). To correlate T cell responses with antibody responses, they analyzed several plasma-derived parameters such as IgG levels, neutralizing antibody levels, and inflammatory mediator levels. Result is,Spike protein IgG levels are strongly correlated with neutralizing antibody activity.

They screened 408 potential epitopes of CD8 + T cells across six human leukocyte antigen (HLA) alleles. As a result, 52 unique hits (peptide reactivity) distributed in 132 epitopes of SARS-CoV-2 were detected. Almost all donors showed an immune response mediated by CD8 + T cells, and over 40% of donors showed 5 or more different SARS-CoV-2 specificities. They also observed that most of the unique hits were directed at non-structural SARS-CoV-2 proteins such as NSP, PLP and ORF3a.

The most common hits were detected for spike proteins and ORF3a. However, the frequency of nucleocapsid-specific CD8 + T cells was significantly higher than that of spike and nonstructural protein-specific T cells. Overall, 6 of 14 different epitopes (per HLA allele) showed T cell-specific reactivity. These findings indicate that COVID-19-recovered patient CD8 + T cells can recognize a wide range of epitopes across a variety of viral proteins.

Regarding the phenotypic characteristics of T cells, scientists have found that the majority of SARS-CoV-2 specific T cells have similar profiles that differ from those of influenza, Epstein-Barr virus, and cytomegalovirus-specific T cells. Observed to share (control group). In addition, SARS-CoV-2 specific T cells exhibited stem cell memory and translocated memory cell-2 (TM2) phenotypes.

Regarding T cell proliferation, high prevalence SARS-CoV-2 specific T cells were associated with late differentiation, whereas low prevalence SARS-CoV-2 specific T cells were associated with early differentiation. Was. The ability of T-stem cell memory cells to differentiate into different subsets of T-memory cells may be associated with long-term protection against SARS-CoV-2 in COVID-19-recovered patients.

Regarding the relationship between inflammation, antibody-mediated immune response, and T-cell-mediated immune response, scientists observed an increase in SARS-CoV-2-specific T cell response during COVID-19 resolution. In addition, higher frequencies of T cells with final differentiation and activation markers correlated with longer recovery times. This indicates that SARS-CoV-2 specific T cell proliferation and progressive differentiation correlate with recovery time. A negative correlation between inflammation and recovery time was indicated by a decrease in plasma cytokine levels over time.

Overall, this study provides new insights into SARS-CoV-2 specific T cell response patterns in COVID-19-recovered patients and helps identify new viral targets for drug discovery or vaccine development.

*Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.