Generation of HPV E782-90 from natural precursors is impaired in CD8/TILlow ERAP1 allotype combinations. Generation of HPV E782-90 from natural precursors.

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Generation of HPV E782-90 from natural precursors is impaired in CD8/TILlow ERAP1 allotype combinations. Generation of HPV E782-90 from natural precursors is impaired in CD8/TILlow ERAP1 allotype combinations. E1KO 293T cells were transfected with ERAP1 allotype combinations from CD8/TILhigh, CD8/TILmoderate, and CD8/TILlow or the nonfunctional active site mutant, E320A, together with minigenes encoding final LV9 or extended precursors D-LV9 or ED-LV9 and assessed for trimming activity by the activation of BE7A2Z. A, Representative line graphs showing the trimming activity of selected ERAP1 allotype combinations from the 3 CD8/TIL groups. B and C, The relative maximum LV9 response of ERAP1 allotype combinations from each group, where each symbol represents an individual ERAP1 allotype combination transfection. Trimming activity toward a single amino acid extension (D-LV9; B) and a double amino acid extension (ED-LV9; ****, P ≤ 0.0001; **, P ≤ 0.01; C). D and E, The relative maximum LV9 response of each individual ERAP1 allotype combination from CD8/TILhigh (black), CD8/TILmoderate (gray), and CD8/TILlow (white) toward D-LV9 (D) and ED-LV9 (E). Data pooled from three independent experimental repeats ± SEM. Emma Reeves et al. Cancer Immunol Res 2019;7:1202-1213 ©2019 by American Association for Cancer Research