RESUMO
Understanding the hallmarks of the immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed antibody and T cell reactivity in convalescent COVID-19 patients and healthy donors sampled both prior to and during the pandemic. Healthy donors examined during the pandemic exhibited increased numbers of SARS-CoV-2-specific T cells, but no humoral response. Their probable exposure to the virus resulted in either asymptomatic infection without antibody secretion or activation of preexisting immunity. In convalescent patients, we observed a public and diverse T cell response to SARS-CoV-2 epitopes, revealing T cell receptor (TCR) motifs with germline-encoded features. Bulk CD4+ and CD8+ T cell responses to the spike protein were mediated by groups of homologous TCRs, some of them shared across multiple donors. Overall, our results demonstrate that the T cell response to SARS-CoV-2, including the identified set of TCRs, can serve as a useful biomarker for surveying antiviral immunity.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Epitopos de Linfócito T/metabolismo , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Adolescente , Adulto , Anticorpos Antivirais/metabolismo , Infecções Assintomáticas , Células Cultivadas , Convalescença , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Imunidade , Memória Imunológica , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Pandemias , Receptores de Antígenos de Linfócitos T/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto JovemRESUMO
The tumor suppressor p53 as the "guardian of the genome" plays an essential role in numerous signaling pathways that control the cell cycle, cell death and in maintaining the integrity of the human genome. p53, depending on the intracellular localization, contributes to the regulation of various cell death pathways, including apoptosis, autophagy and necroptosis. Accumulated evidence suggests that this function of p53 is closely involved in the process of cancer development. Here, present knowledge concerning a p53-autophagy-metastasis link, as well as therapeutic approaches that influence this link, are discussed.