Fig. 6

Enhanced recognition of TL9 escape by B*81:01-derived and B*42:01-derived dual-reactive TCR clones. The ability of each TCR clone to respond to HIV-1 escape mutants was determined by comparing its recognition profile to a panel of 19 naturally occurring subtype C TL9 variants, found at a prevalence of ~0.1% or greater in the LANL HIV Sequence Database (HIV Databases; http://www.hiv.lanl.gov). Recognition breadth for each TCR is illustrated as a SequenceLogo, demonstrating variable responsiveness toward relevant TL9 mutations located primarily at epitope positions 3 and 7. Mono-reactive TCR from B*42:01 expressing individuals displayed narrower profiles that recognized TL9 variants at either position 7 (7A10, a) or position 3 (13A10, b), whereas public dual-reactive B*42:01-derived clones (c–e) and B*81:01-derived clones (f–h) demonstrated broader ability to recognize TL9 variants at both positions 3 and 7. To account for constraints on TL9 escape, epitope variants were displayed using pie charts where the size of each wedge is proportional to variant frequency in circulating subtype C isolates (i–p). Serine at position 7 (S7), serine at position 3 (S3), and threonine at position 3 (T3) accounted for the majority (55%) of population-level variation. For each chart, the wedge is shaded in red (R) if the TCR responded to the escape mutant or in yellow (Y) if the TCR recognized all transitional mutations required to generate that escape mutant from consensus TL9. The sum of all red wedges is displayed under each chart as the total percentage of Variant Epitope Recognition and the sum of all shaded wedges, red plus yellow, is displayed as the total percentage of Escape Pathway Recognition, where recognition of all circulating TL9 variants would be 100%. Overall, B*81:01-derived TCR (n–p) and public dual-reactive B*42:01-derived TCR (k–m) displayed better ability to cross-recognize circulating TL9 escape variants and pathways compared to mono-reactive B*42:01-derived clones (i–j)