Immunitrack has performed the most comprehensive HLA restriction study of SARS-CoV-2 Spike-derived epitopes to date. In total, 1,200 9-mers overlapping by 8 amino acids were screened for binding to 9 HLA I and 10 HLA II alleles (Figure 1). Multiple epitopes have been validated, as outlined in Table 1.
Since T cell responses are likely to differ across ethnicities as a result of the polymorphic nature of HLA I and II receptors, our unique and broad dataset enables a much more in-depth CD4+ and CD8+ T cell study of patient immune responses to SARS-CoV-2 and vaccination. As an example, one recent study published in Nature of CD4+ and CD8+ stimulating epitopes from 32 recovered COVID-19 patients revealed 18 T cell epitopes that gave rise to either CD4+, CD8+, or both CD4+ and CD8+ responses.1 Interestingly, we could HLA-restrict 9-mer minimal epitopes from all but one of the T cell epitopes identified in that study (Table 1).
This report contains a unique HLA restriction dataset that can be applied to study how various epitopes may be linked to patient outcomes, and it also creates an opportunity to use tetramers for isolation and characterisation of T cells, in a way that has not been possible before now.
Interestingly, when comparing our stability data with peptides predicted to be presented by various HLA I alleles, we find that there is a large number of false positives (predicted high affinity but not stable) but also numerous false negative datapoints (predicted low affinity but high stability) (Figure 2).
Figure 3 illustrates the stability output of all +1,200 peptides from Spike for all HLA II alleles investigated in this study.
Figure 1: 1,200 9 mers overlapping by 8 amino acids were screened for their propensity for stable binding to 10 HLA I and 11 HLA II alleles using NeoScreen.
Table 1: Adopted from Peng et al. The following 15-mer peptides from Spike were shown to contain T cell epitopes capable of stimulating PBMCs from COVID-19-infected individuals. We have extended the original table with two columns to the right showing where we could map the 15-mer peptides to one or more HLA I and/or HLA II 9-mers.
Figure 2: Measured stability of all possible Spike COVID-19 9-mers versus predicted affinity on 9 common HLA I alleles. All peptides with measured stability higher than 40% are present in the CD8+ peptide kit. Please note that for some alleles, e.g., A*0101, A*0201, A*0301 and A*1101, there is a reasonable to good correlation between affinity predictions and stability measurements.
Figure 3: Measured stability of all possible Spike COVID-19 9-mers on 10 common HLA II alleles. For the CD4+ peptide kit the selected 9-mers were extended to 11-13-mers, all peptides with measured stability higher than 40% are present in the peptide kit, and for DP401 the threshold was set slightly lower.
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