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. 2020 Jan 17:10:2986.
doi: 10.3389/fimmu.2019.02986. eCollection 2019.

HLA-H: Transcriptional Activity and HLA-E Mobilization

François Jordier  1   2 , Delphine Gras  3 , Maria De Grandis  1   2 , Xavier-Benoît D'Journo  4 , Pascal-Alexandre Thomas  4 , Pascal Chanez  3   5 , Christophe Picard  1   2 , Jacques Chiaroni  1   2 , Julien Paganini  6 , Julie Di Cristofaro  1   2
Affiliations

HLA-H: Transcriptional Activity and HLA-E Mobilization

François Jordier et al. Front Immunol. .

Abstract

Little attention is paid to pseudogenes from the highly polymorphic HLA genetic region. The pseudogene HLA-H is defined as a non-functional gene because it is deleted at different frequencies in humans and because it encodes a potentially non-functional truncated protein. However, different studies have shown HLA-H transcriptional activity. We formerly identified 13 novel HLA-H alleles, including the H*02:07 allele, which reaches 19.6% in East Asian populations and encodes a full-length HLA protein. The aims of this study were to explore the expression and possible function of the HLA-H molecule. HLA-H may act as a transmembrane molecule and/or indirectly via its signal peptide by mobilizing HLA-E to the cell surface. We analyzed HLA-H RNA expression in Peripheral Blood Mononuclear Cells (PBMC), Human Bronchial Epithelial Cells (HBEC), and available RNA sequencing data from lymphoblastoid cell lines, and we looked to see whether HLA-E was mobilized at the cell surface by the HLA-H signal peptide. Our data confirmed that HLA-H is transcribed at similar levels to HLA-G. We characterized a hemizygous effect in HLA-H expression, and expression differed according to HLA-H alleles; most interestingly, the HLA-H*02:07 allele had the highest level of mRNA expression. We showed that HLA-H signal peptide incubation mobilized HLA-E molecules at the cell surface of T-Lymphocytes, monocytes, B-Lymphocytes, and primary epithelial cells. Our results suggest that HLA-H may be functional but raises many biological issues that need to be addressed.

Keywords: HLA-E; HLA-H; expression; pseudogene; signal peptide.

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Figures

Figure 1
Figure 1
HLA-H expression in PBMC and HBEC (dCt: delta of cycle threshold, expression quantified by Q-PCR normalized by ACTB endogenous gene).
Figure 2
Figure 2
HLA-H reads according to HLA-H alleles in hemizygous samples for HLA-H in RNA-sequencing data from the 1000 Genomes Project.
Figure 3
Figure 3
Percentage of PBMC overexpressing HLA-E compared with DMSO (defining M2) after 1, 2, 4, and 6 h of peptide incubation.
Figure 4
Figure 4
PBMC HLA-E overexpression after 1, 2, 4, and 6 h of peptide incubation (gated cells in M2 >1%) compared with DMSO.
See this image and copyright information in PMC

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