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 3
Escape patterns associated with HLA- A*66:01/A*68:01.
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; escaping anchor position = bold-face font residue in the peptide; compensatory position = underlined residue in the peptide. A) Toggling between predicted escape and the Wuhan residue at second anchor position of the HLA- A*68:01 binding peptide ’94-STEKSNIIR-102’. The escape variant 95I also binds to the same HLA allele. DRB1*04:01 is associated with same T95I escape in 90-VYFASTEKS-98 (15mer = 87-NDGVYFASTEKSNII). B) HLA-A*66:01 and A*68:01 drive escape at 408, compensation 405N alone fails, but compensation with escape increase. DQA1*01:02-DQB1*06:02 binds the emerged 408S escape with 405N compensation. C) Proportions of predicted toggling escape at second anchor position of 370-NSASFSTFK-378 peptide binder to HLA- A*03:01 and A*66:01, with compensatory mutation sites 373 and 375. The escape mutation S371F dominates with additional compensation of T376A. D) Toggling between predicted escape and the Wuhan residue at C-term anchor position for the HLA- A*03:01 and A*66:01 binding peptide ’409-QIAPGQTGK-417’. The escape variant 417N is not a binder. E) N440K predicted reversion of zoonotic immune escape. The variant 440K is a binding C-term anchor motif for HLA- A*03:01/ A*66:01/ A*68:01. F) HLA-A*02:06/ A*66:01/ A*68:01 bind to the 769V variant. Wuhan likely zoonotic escape, with sporadic reversion attempts. DQA1*01:02-DQB1*06:02 also binds to 769V variant but DRB1*04:01 binds to Wuhan in overlapping 764-NRALTGIAV-772 (15mer = 761-TQLNRALTGIAVEQD). N-terminal N764K anchor mutation also observed and both binders to HLA-II. G) N856K attempted reversion of zoonotic immune escape at a cryptic anchor motif for HLA-B*08:01. The variant peptide ‘852-AQKFKGLTV-860’ is a strong binder but the Wuhan peptide is not a binder. The variant is also a C-term anchor for an overlapping A*66:01 binding peptide 848-DLICAQKFK-856.