Human leukocyte antigen (HLA)-E plays a role in immune tolerance induction and its transport to the cell surface is limited and dependent on the availability of HLA class I signal peptide. The role of HLA-G in regulating HLA-E surface localization remains controversial. The aim of our study was to clarify whether full-length and truncated HLA-G isoforms regulate HLA-E surface localization. Using a retroviral expression system and flow cytometric analysis, we found that surface HLA-E levels were significantly higher in HLA-G1 (34.1±4.4%, p<0.005) and -G3 (15.3±1.8%, p<0.04) versus empty vector (9.0±1.0%) transductants. Biotinylation and Western blot studies revealed HLA-E surface protein was increased by 4.5- and 1.3-fold in HLA-G1 and -G3 versus empty vector transductants. Although no significant differences in transcript and protein levels were detected between HLA-G1 and -G3 transductants, surface levels of HLA-G1 were 2.5-fold higher than HLA-G3 by flow cytometric analysis and Western blotting. Taken together, our data demonstrate that full-length HLA-G1 and truncated -G3 differentially increase HLA-E surface localization.
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