Influence of HLA Class II Polymorphism on Predicted Cellular Immunity Against SARS-CoV-2 at the Population and Individual Level

Abstract

Development of adaptive immunity after COVID-19 and after vaccination against SARS-CoV-2 is predicated on recognition of viral peptides, presented on HLA class II molecules, by CD4+ T-cells. We capitalised on extensive high-resolution HLA data on twenty five human race/ethnic populations to investigate the role of HLA polymorphism on SARS-CoV-2 immunogenicity at the population and individual level. Within populations, we identify wide inter-individual variability in predicted peptide presentation from structural, non-structural and accessory SARS-CoV-2 proteins, according to individual HLA genotype. However, we find similar potential for anti-SARS-CoV-2 cellular immunity at the population level suggesting that HLA polymorphism is unlikely to account for observed disparities in clinical outcomes after COVID-19 among different race/ethnic groups. Our findings provide important insight on the potential role of HLA polymorphism on development of protective immunity after SARS-CoV-2 infection and after vaccination and a firm basis for further experimental studies in this field.

SARS-CoV-2 Epitope Presentation by Class II HLA Genotypes Common in North American Populations: A Proposed Computational Approach for Vaccine Efficacy Evaluation

“…In opposition to Copley et al's conclusion that all ethnic groups have similar HLA II antigen presentation potential,(18) the findings presented here demonstrated variability in vaccine effectiveness based on different antigen presentation patterns for all vaccine types investigated. This discrepancy may result from differences in methodology.…”

Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role of TP53, ABO, APOE, ACE2, HLA-A, and CRP genes

“…The association between the HLA system and COVID-19 prognosis has been thoroughly investigated, recognizing potential HLA carriers associated to higher risk of death ( Hamming et al, 2004 ; Grifoni et al, 2020 ; Huang et al, 2020 ; Liao et al, 2020 ; Pretti et al, 2020 ; Tay et al, 2020 ; Wang et al, 2020 ; Zhang et al, 2020 ). Although recent studies suggested that HLA polymorphisms might unlikely account for the wide disparities in COVID-19 prognosis, they concluded on the potential role of HLA polymorphisms on the development of SARS-CoV-2 immunity also after vaccination by evaluating the association between specific HLA variants and vaccine response ( Copley et al, 2021 ; Shukla et al, 2022 ). Even though a first extensive report excluded the HLA impact on the immunoglobulin level fluctuation and duration ( Ragone et al, 2021 ), particular attention has been later directed toward a selected locus ( HLA-A*03:01 ) associated to a weak antibody response and negative side effects after Pfizer–BioNTech vaccine ( Bolze et al, 2022 ; Crocchiolo et al, 2022 ).…”

HLA repertoire of 115 UAE nationals infected with SARS-CoV-2

“…NetMHCpan 4.1 server [35] is a validated algorithm for T-cell epitope prediction and has been recently updated. A combination of binding affinity thresholds that offers the best precision and specificity was used [35,48]. However, it is important to acknowledge the limitation of this computational method.…”

“…However, it is important to acknowledge the limitation of this computational method. The peptide binding recognition is complex and is affected by many factors, including the relative expression of individual viral proteins [48]. Furthermore, there is currently limited data on experimentally determined SARS-CoV-2 immunogenic T-cell epitope and peptide HLA restriction [48], and our analysis relied on the available information in published literature.…”