Peptide-induced HLA-E expression in human PBMCs is dependent on peptide sequence and the HLA-E genotype.
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.
Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands.
N
N
Lauterbach
L
L
Wieten
H E
HE
Popeijus
J
J
Vanderlocht
P M H
PM
van Zon
C E M
CE
Voorter
M G J
MG
Tilanus
D000595:Amino Acid Sequence; D018834:Chaperonin 60 / Q000737:chemistry / Q000276:immunology; D003587:Cytomegalovirus / Q000737:chemistry / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D005838:Genotype; D015235:HLA-B Antigens / Q000737:chemistry / Q000276:immunology; D015236:HLA-C Antigens / Q000737:chemistry / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D000097625:HLA-E Antigens
D018834:Chaperonin 60; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D024101:Mitochondrial Proteins; D010455:Peptides; D012333:RNA, Messenger; D000097625:HLA-E Antigens; C060293:HSPD1 protein, human
cytomegalovirus (CMV); human leukocyte antigen (HLA)-E expression; human leukocyte antigen (HLA)-E polymorphism; peptide; transplantation