T-cell COVID-19 Atlas | Epsilon GH/452R.V1 (B.1.429+B.1.427)

Summary

This strain contains 11 protein-level mutations:

• 4 mutations in Spike protein: S13I, W152C, L452R, D614G
• 1 mutation in N protein: T205I
• 2 mutations in NS3 protein: Q57H, A99V
• 1 mutation in NS9c protein: L52F
• 1 mutation in NSP2 protein: T85I
• 1 mutation in NSP12 protein: P323L
• 1 mutation in NSP13 protein: D260Y

We identified all possible linear viral peptides affected by these mutations. Whenever it was possible, we matched the reference peptide with the mutated one. For example, D -> L mutation transformed SDNGPQNQR to SLNGPQNQR. Cases when it was not meaningful included deletions and insertions at the flanks of the peptide, e.g., HV deletion in NVTWFHAIHV peptide.

Then, we predicted binding affinities between the selected peptides and frequent HLA alleles. Predictions were made with NetMHCpan-4.1 and NetMHCIIpan-4.0. The binding affinities were classifies into three groups:

1. Tight binding (IC50 affinity ≤ 50 nM)
2. Moderate binding (50 nM < IC50 affinity ≤ 500 nM)
3. Weak/no binding (IC50 affinity > 500 nM)

Here we report HLA-peptide interactions whose affinity was altered by at least two folds. Note that mutations with empty set of altered interactions are not showed.

The total number of interactions between HLA-B*27:05 and peptides affected by the mutations

Weaker binding was not found, while stronger binding was found for 7 entries. There are 43 tight binders for the HLA-B*27:05 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 0 of them became non-tight binders (0.0%) and 3 novel tight binders appeared (6.8%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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L452R

Reference DDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGS ||||||||||||||||||||||||| ||||||||||||||||||||||||| Mutated DDFTGCVIAWNSNNLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGS

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Allele	Reference peptide	Mutated peptide	Reference affinity (IC50, nM)	Mutated affinity (IC50, nM)
HLA-B*27:05	YLYRLFRK	YRYRLFRK	9806	50
HLA-B*27:05	YLYRLFRKS	YRYRLFRKS	13862	117
HLA-B*27:05	YLYRLFRKSNLK	YRYRLFRKSNLK	2218	22
HLA-B*27:05	YLYRLFRKSNLKP	YRYRLFRKSNLKP	13004	347
HLA-B*27:05	YLYRLFRKSNLKPF	YRYRLFRKSNLKPF	7101	214
HLA-B*27:05	YLYRLFRKSNL	YRYRLFRKSNL	1360	48
HLA-B*27:05	LYRLFRKSNL	RYRLFRKSNL	932	123