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 5
Zoonosis related 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; A) N501Y predicted reversion of zoonotic immune escape at C-term anchor position of a supermotif in the HLA- B*15:16/ B*15:17/ B*57:01/ B*58:01/A*03:01 binding variant peptide ‘493-QSYGFQPTY-501’. The mutation has toggling compensation while it also acts as a compensation for an overlapping peptide 495-YGFQPTNGV-503. DRB1*01:01 binds N501 and the variant 501Y, escape is at the compensatory positions 496S and 498R, 498 is an anchor in 495-YGFQPTNGV-503 (15mer = 492-LQSYGFQPTNGVGYQ). B) L981F attempted escape mutation or reversion of zoonotic escape mutation at C-term of 973-ISSVLNDIL-981 peptide. The variant is a strong binder to B*58:01/B*57:02. The Wuhan peptide was predicted as a weak binder to same alleles but in absence of known anchor residue motif. DRB1*11:04 also binds same Wuhan and variant on the N-term anchor in 981-LSRLDKVEA-989 (15mer = 978-NDILSRLDKVEAEVQ). C) A701V predicted attempted reversion of a zoonotic immune escape at C-term anchor position of 693-IAYTMSLGV-701 variant peptide with a strong binding motif for HLA- B*51:01/ B*51:02/ B*51:03 alleles. The Wuhan peptide is not a binder to any HLA. DRB1*07:01 binds both Wuhan (weak) and variant (strong) in C-term anchor of 693-IAYTMSLGA -701 (15mer = 690-QSIIAYTMSLGAENS).