HLA-H: Transcriptional Activity and HLA-E Mobilization

François Jordier (1, 2) , Delphine Gras (3) , Maria de Grandis (1, 2) , Xavier-Benoit d'Journo (4) , Pascal-Alexandre Thomas (5) , Pascal Chanez (3) , Christophe Picard (6, 1) , Jacques Chiaroni (6, 1) , Julien Paganini , Julie Di Cristofaro (1, 2)

1 ADES - Anthropologie bio-culturelle, Droit, Ethique et Santé
2 EFS - Etablissement Français du Sang Provence-Alpes Côte-d'Azur et Corse
3 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
4 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
5 CHU Marseille
6 EFS - Alpes-Méditerranée - Etablissement Français du Sang - Alpes-Méditerranée

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.

Mots clés: expression; HLA-E; HLA-H; signal peptide; pseudogene

Domaines: Immunologie; Génomique, Transcriptomique et Protéomique [q-bio.GN]

François Jordier, Delphine Gras, Maria de Grandis, Xavier-Benoit d'Journo, Pascal-Alexandre Thomas, et al.. HLA-H: Transcriptional Activity and HLA-E Mobilization. Frontiers in Immunology, 2020, 10, pp.2986. ⟨10.3389/fimmu.2019.02986⟩. ⟨hal-02493948⟩