Population-level toggling of T cell immune escape at human leukocyte antigen anchor residues in SARS-CoV-2 Spike proteins, in an ethnically diverse population region
Fig 4
Escape patterns associated with other different HLA alleles.
The proportions are shown as follows in all graphs: Wuhan residue = solid grey area; predicted escape variant = dotted area; predicted compensatory mutations = different styles of line graphs; insertions = dotted bar graphs; escaping anchor position = bold-face font residue on the peptide; compensatory position = underlined residue on the peptide. A) HLA-B*08:01 binds Wuhan and both P681R/H escape variants including the later N679K compensation. B*56:01 binds the overlapping Wuhan peptide and a short-lived A688V C-term escape. Peptide overlaps with the C-term of DRB5*01:01 motif and 681 is adjacent to the C-term anchor in 674-YQTQTNSPR-682 (15mer = 671-CASYQTQTNSPRRAR), variants Q675H & H677Q, T678I are also binders. B) Toggling of attempted escape variants driven by B*27:02 and B*27:03 which both bind to the Wuhan peptide and 346T variant. B*27:02 also binds to the 346K variant. C) Proportions of predicted escape, reversion and compensation at C-terminal anchor position for HLA- A*02:05 binding peptide ‘10-LVSSQCVNL-18’. D) HLA-A*02:05 and several A*02 type alleles and/or numerous C alleles drive escape but also bind escape variant due to a supermotif. E) Toggling between predicted escape and the Wuhan residue at C-term anchor position for the HLA- A*02:05, A*02:06, A*02:14 and A*30:01 binding peptide’444-KVGGNYNYL-452’. The escape variant 452R is a binder to A*30:01, A*03:01 and A*68:01. F) Proportions of predicted escape V213G and fixation at second anchor of 212-LVRDLPQGF-220 peptide binder to HLA-B*15:02 and B*07:02, with toggling of compensatory mutation sites L212I/S and D215G within the peptide. A 215-EPE-217 insertion during wave-4 is a potential escape mechanism. DQA1*01:02-DQB1*06:02 binds 215G compensatory mutation in variant 207-HTPINLVRG-215 (15mer = 204-YSKHTPINLVRGLPQ). G) Overlapping Wuhan peptides. C-term F490S mutations short-lived and binds A*24:02/A*26:01. Compensation toggling between E484K/A + T478K. Wuhan and compensations are binders to B*07:02 or B*15:08 or B*35:01. Peptide 478-TPCNGVEGF-486 has C-term F486V escape from B*15:08/B*35:01 motifs.