Data for: Endo-lysosomal assembly variations among Human Leukocyte Antigen class I (HLA-I) allotypes
Data files
Feb 19, 2023 version files 17.94 GB
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Fig_1_-_6-30-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_7-12-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_7-15-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_7-22-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_7-25-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_7-28-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_7-7-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_8-10-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_8-18-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_8-24-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_8-29-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_9-1-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_9-3-22_moDC_bafilomycin_time_course.zip
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Fig_1_-_9-6-22_moDC_bafilomycin_time_course.zip
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Fig_1_2_4_-_1-14-22_moDC_baf_peptide_receptivity.zip
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Fig_1_2_4_-_1-21-22_moDC_baf_peptide_receptivity.zip
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Fig_1_2_4_-_3-24-21_moDC_peptide_receptivity.zip
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Fig_1_2_4_-_3-28-21_moDC_peptide_receptivity.zip
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Fig_1_2_4_-_4-11-21_moDC_peptide_receptivity.zip
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Fig_1_2_4_-_8-16-22_moDC_baf_peptide_receptivity_HC10.zip
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Fig_1_2_4_-_8-22-22_moDC_baf_peptide_receptivity_HC10.zip
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Fig_1_2_4_-_8-24-22_moDC_baf_peptide_receptivity_HC10.zip
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Fig_1_2_4_-_8-29-22_moDC_baf_peptide_receptivity_HC10.zip
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Fig_1_2_4_-_8-31-22_moDC_baf_peptide_receptivity_HC10.zip
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Fig_1_4_4S1_-_10-26-20_moDC_inhibitor_time_course.zip
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Fig_1_4_4S1_-_8-28-20_moDC_inhibitor_time_course.zip
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Fig_1_4_4S1_-_8-7-20_moDC_inhibitor_time_course.zip
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Fig_1_4_4S1_-_8-8-20_moDC_inhibitor_time_course.zip
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Fig_1_4_4S1_-_9-17-20_moDC_inhibitor_time_course.zip
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Fig_1_4_4S1_-_9-4-20_moDC_inhibitor_time_course.zip
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Fig_1_4S1_-_7-20-22_moDC_BBM1_peptide_receptivity.zip
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Fig_1_4S1_-_7-27-22_moDC_BBM1_peptide_receptivity.zip
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Fig_1_4S1_-_8-18-22_moDC_baf_peptide_receptivity_BBM1.zip
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Fig_1_4S1_-_8-22-22_moDC_baf_peptide_receptivity_BBM1.zip
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Fig_1_4S1_-_8-24-22_moDC_baf_peptide_receptivity_BBM1.zip
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Fig_1_4S1_-_8-29-22_moDC_baf_peptide_receptivity_BBM1.zip
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Fig_1_4S1_-_8-31-22_moDC_baf_peptide_receptivity_BBM1.zip
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Fig_1_4S1_-_9-1-22_moDC_baf_peptide_receptivity_BBM1.zip
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Fig_1S1_-_2-16-22_moDC_HLA-C_surface_total.zip
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Fig_1S1_-_3-15-22_moDC_HLA-C_surface_total.zip
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Fig_2_-_3-2-21_moDC_peptide_receptivity.zip
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Fig_2_-_4-26-21_moDC_peptide_receptivity.zip
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Fig_2_-_4-27-21_moDC_peptide_receptivity.zip
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Fig_2_-_5-17-21_moDC_peptide_receptivity.zip
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Fig_2_-_5-5-21_moDC_peptide_receptivity.zip
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Fig_2_-_6-13-21_moDC_peptide_receptivity.zip
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Fig_2_-_7-12-22_HLA-B_HC10_bead_pH_peptide_exchange.zip
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Fig_2_-_7-28-22_HLA-B_bead_pH_peptide_exchange.zip
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Fig_2_-_7-29-22_HLA-B_bead_pH_peptide_exchange.zip
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Fig_2_-_7-8-22_HLA-B_HC10_bead_pH_peptide_exchange.zip
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Fig_3_3S1_-_10-16-20_D148_monocyte_Bw6-EEA1.zip
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Fig_3_3S1_-_10-16-20_D187_monocyte_Bw6-EEA1.zip
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Fig_3_3S1_-_10-7-20_D166_moDC_Bw6-EEA1.zip
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Fig_3_3S1_-_10-7-20_D166_moDC_Bw6-LAMP1.zip
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Fig_3_3S1_-_10-7-20_D166_moDC_Bw6-Rab11.zip
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Fig_3_3S1_-_10-7-20_D187_moDC_Bw6-EEA1.zip
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Fig_3_3S1_-_10-7-20_D187_moDC_Bw6-LAMP1.zip
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Fig_3_3S1_-_10-7-20_D187_moDC_Bw6-Rab11.zip
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Fig_3_3S1_-_5-20-19_D187_monocyte_Bw6-LAMP1.zip
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Fig_3_3S1_-_5-20-19_D24_monocyte_Bw6-LAMP1.zip
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Fig_3_3S1_-_5-20-19_D55_monocyte_Bw6-LAMP1.zip
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Fig_3_3S1_-_6-17-19_D136_monocyte_Bw6-LAMP1.zip
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Fig_3_3S1_-_6-17-19_D178_monocyte_Bw6-LAMP1.zip
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Fig_3_3S1_-_6-27-19_D136_monocyte_Bw6-Rab11-Arf6.zip
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Fig_3_3S1_-_6-27-19_D178_monocyte_Bw6-Rab11-Arf6.zip
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Fig_3_3S1_-_7-24-19_D130_monocyte_Bw6-Arf6-Rab11.zip
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Fig_3_3S1_-_7-24-19_D130_monocyte_Bw6-EEA1-TAP1.zip
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Fig_3_3S1_-_7-24-19_D210_monocyte_Bw6-Arf6-Rab11.zip
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Fig_3_3S1_-_7-24-19_D210_monocyte_Bw6-EEA1-TAP1.zip
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Fig_3_3S1_-_8-11-20_D198_moDC_Bw6-EEA1.zip
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Fig_3_3S1_-_8-11-20_D198_moDC_Bw6-LAMP1.zip
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Fig_3_3S1_-_8-11-20_D198_moDC_Bw6-Rab11.zip
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Fig_3_3S1_-_8-11-20_D24_moDC_Bw6-EEA1.zip
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Fig_3_3S1_-_8-11-20_D24_moDC_Bw6-LAMP1.zip
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Fig_3_3S1_-_8-11-20_D24_moDC_Bw6-Rab11.zip
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Fig_3_3S1_-_8-11-20_D55_moDC_Bw6-EEA1.zip
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Fig_3_3S1_-_8-11-20_D55_moDC_Bw6-LAMP1.zip
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Fig_3_3S1_-_8-11-20_D55_moDC_Bw6-Rab11.zip
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Fig_3_3S1_4_4S1_-_1-20-21_D187_moDC_untreated_Bw6-LAMP1.zip
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Fig_3_3S1_4_4S1_-_3-22-21_D94_moDC_untreated_Bw6-LAMP1.zip
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Fig_3_3S1_4_4S1_-_3-26-21_D168_moDC_untreated_Bw6-LAMP1.zip
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Fig_3_3S1_4_4S1_-_3-26-21_D237_moDC_untreated_Bw6-LAMP1.zip
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Fig_3_3S1_4S1_-_1-20-21_D187_moDC_untreated_Bw6-Rab11.zip
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Fig_3_3S1_4S1_-_3-22-21_D94_moDC_untreated_Bw6-Rab11.zip
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Fig_3_3S1_4S1_-_3-26-21_D168_moDC_untreated_Bw6-Rab11.zip
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Fig_3_3S1_4S1_-_3-26-21_D237_moDC_untreated_Bw6-Rab11.zip
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Fig_4_-_6-20-19_PBMC_recycling_inhibitors.zip
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Fig_4_-_7-10-19_PBMC_recycling_inhibitors.zip
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Fig_4_-_7-9-19_PBMC_recycling_inhibitors.zip
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Fig_4_-_9-16-19_PBMC_recycling_inhibitors.zip
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Fig_4_-_9-26-19_PBMC_recycling_inhibitors.zip
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Fig_4_4S1_-_1-20-21_D187_moDC_bafilomycin_Bw6-LAMP1.zip
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Fig_4_4S1_-_3-22-21_D94_moDC_bafilomycin_Bw6-LAMP1.zip
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Fig_4_4S1_-_3-26-21_D168_moDC_bafilomycin_Bw6-LAMP1.zip
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Fig_4_4S1_-_3-26-21_D237_moDC_bafilomycin_Bw6-LAMP1.zip
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Fig_4_4S1_-_3-4-20_PBMC_MG132-Baf_treatment.zip
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Fig_4S1_-_1-20-21_D187_moDC_bafilomycin_Bw6-Rab11.zip
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Fig_4S1_-_1-23-20_PBMC_MG132_time_course.zip
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Fig_4S1_-_1-27-20_PBMC_MG132_time_course.zip
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Fig_4S1_-_2-5-20_PBMC_MG132_time_course.zip
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Fig_4S1_-_3-22-21_D94_moDC_bafilomycin_Bw6-Rab11.zip
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Fig_4S1_-_3-26-21_D168_moDC_bafilomycin_Bw6-Rab11.zip
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Fig_4S1_-_3-26-21_D237_moDC_bafilomycin_Bw6-Rab11.zip
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Fig_4S1_-_7-18-22_HLA-B_BBM1_bead_pH_peptide_exchange.zip
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Fig_4S1_-_7-23-22_HLA-B_BBM1_bead_pH_peptide_exchange.zip
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Fig_4S1_-_8-13-22_HLA-B_bead_pH_peptide_exchange.zip
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Fig_4S1_-_8-15-22_HLA-B_bead_pH_peptide_exchange.zip
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Fig_5_-_10-1-21_monocyte_DQ-Ova_time_course.zip
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Fig_5_-_10-20-21_monocyte_DQ-Ova_time_course.zip
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Fig_5_-_10-27-21_moDC_DQ-Ova_time_course.zip
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Fig_5_-_11-11-21_moDC_DQ-Ova_time_course.zip
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Fig_5_-_8-22-21_monocyte_DQ-Ova_time_course.zip
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Fig_5_-_8-27-21_monocyte_DQ-Ova_time_course.zip
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Fig_5_-_9-24-21_moDC_DQ-Ova_time_course.zip
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Fig_5A_-_3-31-21_moDC_antigen_uptake_rate.zip
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Fig_5A_-_4-2-21_moDC_antigen_uptake_rate.zip
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Fig_5A_-_4-2-21_monocyte_antigen_uptake_rate.zip
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Fig_5A_-_4-8-21_monocyte_antigen_uptake_rate.zip
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Fig_6_-_1-26-22_CTL_peptide_titration.zip
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Fig_6_-_1-28-22_CTL_peptide_titration.zip
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Fig_6_-_2-10-22_CTL_peptide_titration.zip
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Fig_6_-_2-11-22_CTL_peptide_titration.zip
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Fig_6_-_5_14_19_monocyte_cross-presentation_assay.zip
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Fig_6_-_5_3_19_monocyte_cross-presentation_assay.zip
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Fig_6_-_6_13_19_monocyte_cross-presentation_assay.zip
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Fig_6_7_-_1-13-21_monocyte_BZLF1_cross-presentation.zip
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Fig_6_7_-_1-20-21_moDC_BZLF1_cross-presentation.zip
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Fig_6_7_-_1-28-22_monocyte_EBNA3A_cross-presentation.zip
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Fig_6_7_-_1-6-21_moDC_BZLF1_cross-presentation.zip
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Fig_6_7_-_10-1-21_monocyte_CTI1_cross-presentation.zip
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Fig_6_7_-_10-13-21_moDC_CTI1_cross-presentation.zip
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Fig_6_7_-_10-26-21_monocyte_CTI1_cross-presentation.zip
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Fig_6_7_-_10-6-21_monocyte_CTI1_cross-presentation.zip
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Fig_6_7_-_10-8-21_moDC_CTI1_cross-presentation.zip
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Fig_6_7_-_10-8-21_monocyte_CTI1_cross-presentation.zip
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Fig_6_7_-_12-16-20_moDC_cross-presentation.zip
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Fig_6_7_-_2-14-22_monocyte_EBNA3A_cross-presentation.zip
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Fig_6_7_-_2-18-22_moDC_BZLF1_cross-presentation.zip
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Fig_6_7_-_2-21-20_monocyte_cross-presentation_assay.zip
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Fig_6_7_-_2-24-22_moDC_EBNA3A_cross-presentation.zip
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Fig_6_7_-_2-26-20_moDC_cross-presentation_experiment.zip
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Fig_6_7_-_2-4-22_moDC_EBNA3A_cross-presentation.zip
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Fig_6_7_-_3-12-20_moDC_cross-presentation_experiment.zip
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Fig_6_7_-_3-17-22_monocyte_EBNA3A_cross-presentation.zip
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Fig_6_7_-_3-22-22_monocyte_EBNA3A_cross-presentation.zip
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Fig_6_7_-_3-24-22_moDC_EBNA3A_cross-presentation.zip
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Fig_6_7_-_3-3-22_moDC_EBNA3A_cross-presentation.zip
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Fig_6_7_-_3-9-20_monocyte_cross-presentation_experiment.zip
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Fig_6_7_-_6-1-21_moDC_cross-presentation.zip
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Fig_6_7_-_8-25-22_monocyte_cross-presentation.zip
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Fig_6_7_-_8-29-20_moDC_cross-presentation_experiment.zip
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Fig_6_7_-_9-13-22_monocyte_cross-presentation.zip
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Fig_6_7_-_9-15-22_moDC_cross-presentation.zip
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Fig_6_7_-_9-15-22_monocyte_cross-presentation.zip
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Fig_6_7_-_9-16-20_monocyte_cross-presentation_experiment.zip
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Fig_6_7_-_9-7-22_moDC_cross-presentation.zip
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Fig_6_7_-_9-8-22_monocyte_cross-presentation.zip
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README.md
Abstract
The extreme polymorphisms of HLA-I proteins enable the presentation of diverse peptides to cytotoxic T lymphocytes (CTL). The canonical endoplasmic reticulum (ER) HLA-I assembly pathway enables presentation of cytosolic peptides, but effective intracellular surveillance requires multi-compartmental antigen sampling. Endo-lysosomes are generally sites of HLA class II assembly, but human monocytes and monocyte-derived dendritic cells (moDCs) also contain significant reserves of endo-lysosomal HLA-I molecules. We hypothesized variable influences of HLA-I polymorphisms upon outcomes of endo-lysosomal trafficking, as the stabilities and peptide occupancies of cell surface HLA-I are variable. Consistent with this model, when the endo-lysosomal pH of moDCs is disrupted, HLA-B allotypes display varying propensities for reductions in surface expression, with HLA-B*08:01 or HLA-B*35:01 being among the most resistant or sensitive respectively, among eight tested HLA-B allotypes. Perturbations of moDC endo-lysosomal pH result in redistribution of HLA-B*35:01, but not HLA-B*08:01, to LAMP1+ compartments and increase HLA-B*35:01 peptide receptivity. These findings reveal the intersection of the vacuolar cross-presentation pathway with a constitutive assembly pathway for some HLA-B allotypes. Notably, cross-presentation of epitopes derived from two soluble antigens was also more efficient for B*35:01 compared to B*08:01, even when matched for T cell response sensitivity, and more affected by cathepsin inhibition. Thus, HLA-I polymorphisms dictate the degree of endo-lysosomal assembly, which can supplement ER assembly for constitutive HLA-I expression and increase the efficiency of cross-presentation.
Methods
Flow Cytometry, Microscopy and T cell assays.
Usage notes
Data can be accessed using FLow Jo and Image J.