Total predicted MHC-I epitope load is inversely associated with population mortality from SARS-CoV-2

Abstract

Polymorphisms in MHC-I protein sequences across human populations significantly impacts viral peptide binding capacity and thus alters T cell immunity to infection. In the present study, we assess the relationship between observed SARS-CoV-2 population mortality and the predicted viral binding capacities of 52 common MHC-I alleles. Potential SARS-CoV-2 MHC-I peptides are identified using a consensus MHC-I binding and presentation prediction algorithm, called EnsembleMHC. Starting with nearly 3.5 million candidates, we resolve a few hundred highly probable MHC-I peptides. By weighing individual MHC allele-specific SARS-CoV-2 binding capacity with population frequency in 23 countries, we discover a strong inverse correlation between predicted population SARS-CoV-2 peptide binding capacity and mortality rate. Our computations reveal that peptides derived from the structural proteins of the virus produce a stronger association with observed mortality rate, highlighting the importance of S, N, M, E proteins in driving productive immune responses.

SARS-CoV-2-specific T cells in infection and vaccination

“…Of note, Spike-specific T cells are highly heterogeneous in different vaccine recipients not only in terms of specificity but also in quantitative terms. Indeed, since T cells recognize short sequences of viral antigens (epitopes) derived from the processing of viral antigens associated with HLA-class I or HLA-class II molecules, it is unsurprising that each individual will be characterized by a distinct fingerprint of T cells that varies in relation to its HLA-class I and Class II profile [ 74 ]. Recent analysis of the number of T cell epitopes already mapped in SARS-CoV-2 infection revealed the extent of such multispecificity [ 75 ].…”

Deciphering Human Leukocyte Antigen Susceptibility Maps From Immunopeptidomics Characterization in Oncology and Infections

“…Hence, these results could help in the selection of suitable bacterial or virus targets for cancer immunotherapy (Riemer, 2021). And more recently, in the last year, immunopeptidomics has also been successfully used to identify SARS-CoV-2 peptides; so then, the relationship between the binding capacity of viral peptides to 52 common MHC-I alleles and the mortality rate has been assessed, resulting in a high inverse relationship between peptides identified from the virus using a personal workflow called Ensemble-MHC (a consensus algorithm for the prediction of MHC-I peptides) and the mortality rate (Wilson et al, 2021). Among these aspects, there is also a close relationship between onco-immunotherapies and infectious disease.…”

Does immune recognition of SARS-CoV2 epitopes vary between different ethnic groups?

“…It is worth further investigation whether a larger pool of MHC-I alleles presenting SARS-CoV2 antigens to CD8+ T cells in the SAS population indeed can be linked to the apparently lower fatality rate in this region. A recent study while reporting an inverse associations between MHC-I epitopes and mortality rates also indicated at this possibility (Wilson et al, 2021). Moreover, any possible relationship of the larger pool of the MHC-II alleles in the EUR population with CD4+ T Cell activation, cytokine production leading to a disproportionate immune response (or a so called "cytokine-storm") will also be intriguing to explore.…”