No abstract

The ongoing COVID-19 pandemic calls for more effective diagnostic tools, and T cell response assessment can serve as an independent indicator of prior COVID-19 exposure while also contributing to a more comprehensive characterization of SARS-CoV-2 immunity. In this study, we systematically assessed the immunogenicity of 118 epitopes with immune cells collected from multiple cohorts of vaccinated, convalescent, and healthy unexposed and SARS-CoV-2 exposed donors. We identified seventy-five immunogenic epitopes, 24 of which were immunodominant. We further confirmed HLA restriction for 49 epitopes, and described association with more than one HLA allele for 14 of these. After excluding two cross-reactive epitopes that generated a response in pre-pandemic samples, we were left with a 73-epitope set that offers excellent diagnostic specificity without losing sensitivity compared to full-length antigens, which evoked a robust cross-reactive response. We subsequently incorporated this set of epitopes into an in vitro diagnostic ‘Corona-T-test’ which achieved a diagnostic accuracy of 95% in a clinical trial. When applied to a cohort of asymptomatic seronegative individuals with a history of prolonged SARS-CoV-2 exposure, this test revealed a lack of specific T cell response combined with strong cross-reactivity to full-length antigens, indicating that abortive infection had occurred in these individuals.

T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. We identified 756 clonotypes specific to nine CD8+ T cell epitopes. Some epitopes were recognized by highly similar public clonotypes. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence.

The article presents the results of the research aimed at building the framework for in- depth analysis of comprehension of implicit meanings in verbal texts. The existing approaches to studying implicit meanings and text comprehension are described, and common features of the cognitive processes underlying text comprehension are highlighted to provide the basis for further research. Different approaches to choosing and processing textual stimuli are also outlined and a model text along with the system of its analysis are proposed. The proposed analysis is based on stylistic and propositional methods. The suggestion is made that studying the way recipients reconstruct different types of elements of implicit meanings on different levels of text structure can allow to gain a better insight in the process of text comprehension. This approach will allow to explore the gradual nature of comprehension in relation with the gradual structure of the text, as well as reveal the cognitive operations underlying text comprehension and the certawein ways readers apply them when building their mental representations of the text. The article also presents the results of analysis of the model stimulus text by a group of experts. The expert group included eight linguists who individually performed the analysis of the text according to the scheme we provided. The results of the experts’ analysis of the text provide support for using it as a model in future research. The obtained results can also be interpreted as evidence for the existence of objective semantic content of the text which imposes restrictions on the multitude of its interpretations.

T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. To identify epitopes that give rise to long-lived T cell memory, we performed ex vivo T cell expansion, MHC-tetramer cell-sorting, and high-throughput sequencing. We identified 756 clonotypes specific to nine known CD8+ T cell receptor (TCR) epitopes. Some epitopes were recognized by highly similar public clonotypes with restricted variable and joining segment usage. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We also tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence. Our study demonstrates the durability of SARS-CoV-2-specific CD8+ memory, and offers important implications for vaccine design.