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Human Leukocyte Antigen (HLA)-E is a low-polymorphic non-classical HLA class I molecule which plays a crucial role in immune surveillance by presentation of peptides to T and natural killer (NK) cells. HLA-E polymorphism is related to HLA-E surface expression and is associated with patient outcome after stem cell transplantation. We aim to investigate the regulation of HLA-E expression level in peripheral blood mononuclear cells (PBMCs) of healthy individuals homozygous for HLA-E*01:01 or HLA-E*01:03, by using a panel of HLA-E binding peptides derived from CMV, Hsp60 and HLA class I. Basal and peptide-induced HLA-E surface expression levels were higher in PBMC from HLA-E*01:03 homozygous subjects as compared to PBMC from HLA-E*01:01 homozygous subjects. HLA-E mRNA levels were comparable between the two genotypes and remained constant after peptide stimulation. HLA-E surface expression seemed to be not only dependent on the HLA-E genotype, but also on the sequence of the peptide as evidenced by the profound difference in HLA-E upregulation with the Hsp60 and the B7 peptide. Our results showed that peptide-induced HLA-E expression is regulated at the posttranscriptional level as extracellular peptide stimulation did not influence RNA expression. This study provides new insights in the mechanism by which HLA-E expression is regulated and underlines a new role for extracellular peptides in inducing HLA-E translation, which may represent a defense mechanism against lytic viral infections and necrosis.

Human leukocyte antigen-E (HLA-E) is a non-classical HLA class I gene that shows a limited degree of polymorphism compared to the classical HLA genes. The HLA-E molecule can bind peptides derived from the leader sequence of various HLA class I alleles and some viral homologues, including CMV. The HLA-E peptide complex can act as a ligand for the CD94/NKG2 receptors expressed on the surface of natural killer cells and T cell subsets. Differences in expression levels between the different HLA-E alleles have been reported and a role for HLA-E polymorphism in stem cell transplantation has been postulated. This chapter focuses on routine technologies for HLA-E typing: the sequence-specific primer-PCR method that uses sequence-specific primers, the PCR sequence-specific oligonucleotides Luminex method, using sequence-specific probes attached to beads and the sequencing-based typing method, where sequencing of the alleles is performed.

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