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First Author:  Gangaev et al. 

Journal/preprint name: Preprint at Research Square 

Paper DOI 

Tags:  Immunology, Bioinformatics 

Summary  

Gangaev et al. aim to provide a CD8 T cell antigen landscape of the full SARS-CoV-2 genome for 10 prominent HLA-I types. By in silico analysis, 50 peptides are selected for each HLA (500 total) and tested against CD8 T cells from 22 severe and critical COVID patients. 9 specific peptides triggered SARS-CoV-2 CD8 T cell responses, 5 unique to SARS-CoV-2 and 4 shared with SARS-CoV-1, none within highly mutable regionsThe majority of CD8 T cell responses (11/16) belonged to HLA-A*01:01 and to epitopes derived to ORF1ab, in which the responses were higher in magnitudeTTDPSFGLGRY (TTD) was the immunodominant epitope for HLA-A*01:01 patients. The TTD CD8-specific response was highly dysfunctional, unable to produce cytokines and based on scRNAseq data, with reduced ability to migrate.  

Research Highlights 

  1.  TTDPSFGLGRY is an immunodominant epitope for the subgroup of patients positive for HLA-A*01:01 

  1. The majority of CD8 T cell responses (11/16) belonged to HLA-A*01:01 and to epitopes derived to ORF1ab, in which the responses were higher in magnitude 

Impact for COVID-19 research:  

  • Description of a new immunodominant epitope for a specific HLA 

Methodologies:  

  • Study Typein vitro, cohort study, in silico, ex vivo. 

  • Important cell lines/viral models used: Clinical samples 

  • Key Techniques: pHLA multimers conjugated to fluorescent dyes to assess CD8 reactivity, FACS, scRNAseq.  

Limitations: 

  • Small cohort with many participants being HLA-A*01:01 

  • Patients were in treatment or not, which may have influenced the activation state of the cells.  

  • HLA-A*01:01 type is highly associated with autoimmune diseases but the authors don’t comment on that. 

  • The authors don’t specify if they found any response with the other peptides incorporated in the study as previously described in the literature, which would be an informative control for the assay.  

  • The analysis of the scRNAseq is very limited and the differences between clusters C3-C6 are not well defined. One of the patients contributes substantially more than the others. 

  • The authors claim that there is no bias in having more peptides from ORF1ab as the contribution is similar to the proteome, but then state that ORF1ab is the least translated ORF of the SARS-CoV-2 genome; which is contradictory.