Abstract
Aim: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019, a global pandemic. There is hence an urgent need for effective approaches to understand the mechanism of viral interaction with immune cells that lead to viral elimination and subsequent long-term immunity. The first, immediate response to the viral infection involves mobilization of native immunity and human leukocyte antigen (HLA) class I mechanisms to kill infected cells and eliminate the virus. The second line of defense involves the activation of HLA class II system for the production of antibodies against the virus which will add to the elimination of the virus and prevent future infections. In a previous study, investigated the relations between SARS-CoV-2 spike glycoprotein (S protein) and HLA class II alleles were investigaed; here report on the relations of the S protein and the open reading frame 1ab (ORF1ab) of SARS-CoV-2 to HLA class I alleles. Methods: An in silico sliding window approach was used to determine exhaustively the binding affinities of linear epitopes of 10 amino acid length (10-mers) to each of 61 common (global frequency ≥ 0.01) HLA class I molecules (17, 24 and 20 from gene loci A, B and C, respectively). A total of 8,354 epitopes were analyzed; 1,263 from the S protein and 7,091 from ORF1ab. Results: HLA-A genes were the most effective at binding SARS-CoV-2 epitopes for both spike and ORF1ab proteins. Good binding affinities were found for all three genes and were distributed throughout the length of the S protein and ORF1ab polyprotein sequence. Conclusions: Common HLA class I molecules, as a population, are very well suited to binding with high affinity to SARS-CoV-2 spike and ORF1ab proteins and hence should be effective in aiding the early elimination of the virus.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a disease that has become a global pandemic
We investigated the relations between two important proteins of the SARS-CoV-2 proteome, and 61 common human leukocyte antigen (HLA) class I alleles
We sought to quantify the binding affinity of suitable fragments of the S protein and open reading frame 1ab (ORF1ab) polyprotein to the 61 HLA class I alleles in an exhaustive manner using the sliding epitope window approach [3, 4]; second, we aimed to assess differences in allele binding affinities between the two proteins, among the three HLA class I genes, and their interaction; and third, we sought to assess the distribution of binding affinities across the sequences of the two proteins
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a disease that has become a global pandemic. The steps following infection include a first phase during which native immunity mechanisms and human leukocyte antigen (HLA) class I molecules (of the A, B, C genes) combat the virus by recruiting cells entered by the virus which is fragmented via proteasomal cleavage to 9-13 amino acid (AA) fragments. HLA class I genes code for cell-surface glycoproteins are expressed on nucleated cells and present on the cell surface those antigen peptides to CD8+ cytotoxic T cells to signal cell destruction, eliminating infected cells. HLA class II molecules (of the HLADR, -DQ and -DP genes) are expressed on professional antigen-presenting cells (e.g., macrophages, dendritic cells) and present endocytosed extracellular antigen peptides to CD4+ T cells to promote B-cell mediated antibody production and immune memory. The HLA region in chromosome 6 is the most highly polymorphic in the human genome resulting in considerable individual and population variability in HLA composition, reflecting the long evolutionary history of exposure to and dealing with elimination and ultimate protection from various pathogens [1, 2]
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