2020
DOI: 10.1101/2020.12.18.423507
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SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes

Abstract: CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control, though direct evidence has been lacking so far. Here, we identified non-synonymous mutations in MHC-I restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV- 2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the cap… Show more

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Cited by 13 publications
(9 citation statements)
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References 50 publications
(15 reference statements)
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“…As a result, this mutation may allow a greater interaction between the spike protein and hACE2 ( 35 ). Thus genetic alterations may impair the host immune system's capacity to recognize and resist the virus ( 36 , 37 ). Certain mutations may enhance viral spread from cell to cell by fusion.…”
Section: Discussionmentioning
confidence: 99%
“…As a result, this mutation may allow a greater interaction between the spike protein and hACE2 ( 35 ). Thus genetic alterations may impair the host immune system's capacity to recognize and resist the virus ( 36 , 37 ). Certain mutations may enhance viral spread from cell to cell by fusion.…”
Section: Discussionmentioning
confidence: 99%
“…Selection of peptides from literature: T cell epitopes from COVID recovered convalescent patients' studies were selected from available vast literatures (14,15,17,28,29,30,32,38). The search was more for CD4+ epitopes as it was found CD8+ epitopes were heavily mutated (causing nonpersistent immunity) in different patients' samples (33). We mostly selected potent epitopes with definite secondary structures as per PDBsum.…”
Section: Methods: Clustal Omega Analyses Of Sars-1 and Sars-2 Spike S...mentioning
confidence: 99%
“…Also, more attention was given on CD4+ TCR epitopes than CD8+. Since the former sequences were found to be more stable than the other as per studies on patients (33). Finally, the designed sequence had 5 epitopes joined by linkers as cytoplasmic region.…”
Section: Introductionmentioning
confidence: 93%
“…This auto-reactivity has been shown to correlate with the severity of clinical outcomes [ 21 ]. There is also evidence SARS-CoV-2 can subvert CD8+ T cell surveillance through escape mutations in MHCI-restricted viral epitopes [ 54 , 55 ]. The longer-term impacts on the immune system are yet unknown, but particularly in light of possible viral/antigenic persistence and the potential for reinfection, we should be concerned about the risk of lasting immune dysfunction and damage.…”
Section: Immune Dysregulationmentioning
confidence: 99%