Question

describe the process of antigen presentation of COVID-19 to CD8+T cells. Include how the virus enters the cells, is processed in the cells, and activates CD8 T cells. 


Answer 1

Covid19 is pandamic disease which is affected by most of the countries. Coronavirus disease (COVID-19) is caused by SARS-COV2 .The large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients to controle the infection spread.

Corona virus primarily targets the human respiratory system. The virus enter the body through droplets containing the virus particle produced form a infrcted person by coughing sneezing and also by body touching with contaminated hands. After 5 to 14 days of incubation period the symptoms become appear. The most common symptoms at onset of COVID-19 illness are fever, cough, and fatigue, while other symptoms include sputum production, headache, haemoptysis, diarrhoea, dyspnoea, and lymphopenia .

A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance. These features may contribute to the wide spread of the virus. Successful intervention strategies must target both the potency of SARS-CoV-2 and its evasiveness.

After the virus enters the cells, its antigen will be presented to the antigen presentation cells(APC), which is a central part of the body’s anti-viral immunity. Antigenic peptides are presented by major histocompatibility complex (MHC; or human leukocyte antigen (HLA) in humans) and then recognized by virus-specific cytotoxic T lymphocytes (CTLs).

Antigen presentation subsequently stimulates the body’s humoral and cellular immunity, which are mediated by virus-specific B and T cells. Similar to common acute viral infections, the antibody profile against SARS-CoV virus has a typical pattern of IgM and IgG production. The SARS-specific IgM antibodies disappear at the end of week 12, while the IgG antibody can last for a long time, which indicates IgG antibody may mainly play a protective role , and the SARS-specific IgG antibodies primarily are S-specific and N-specific antibodies . Comparing to humoral responses, there are more researches on the cellular immunity of coronavirus. The latest report shows the number of CD4+ and CD8+ T cells in the peripheral blood of SARS-CoV-2-infected patients significantly is reduced, whereas its status is excessive activation, as evidenced by high proportions of HLA-DR (CD4 3.47%) and CD38 (CD8 39.4%) double-positive fractions . Similarly, the acute phase response in patients with SARS-CoV is associated with severe decrease of CD4+ T and CD8+ T cells. Even if there is no antigen, CD4+ and CD8+ memory T cells can persist for four years in a part of SARS-CoV recovered individuals and can perform T cell proliferation, DTH response and production of IFN-γ . Six years after SARS-CoV infection, specific T-cell memory responses to the SARS-CoV S peptide library could still be identified in 14 of 23 recovered SARS patients . The specific CD8+ T cells also show a similar effect on MERS-CoV clearance in mice . These findings may provide valuable information for the rational design of vaccines against SARS-CoV-2.