SARS-CoV-2 Virus and

Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.

Class II: Investigation in silico of Binding Affinities for COVID-19 Protection and Vaccine Development

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common -Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a Class II molecule for CD4+ T cell activation by the antigen- molecule complex