High-allelic variability in HLA-C mRNA expression: association with HLA-extended haplotypes.
Human leukocyte antigen (HLA)-C is a clinically relevant transplantation antigen in unrelated hematopoietic stem cell and cord blood transplantation. Furthermore, HLA-C antigens, as ligands for killer immunoglobulin-like receptors expressed on natural killer cells, have a central role in HIV control. Several studies have reported significant correlations between HLA-C mRNA and cell surface expression with polymorphisms in the 5'- and 3'-regions of the HLA-C locus. We determined HLA-C mRNA in blood donors by using locus as well as allele-specific real-time-PCR and focused the analysis on HLA-extended haplotypes. High inter-individual variability of mRNA expression was disclosed. A lower inter-individual variability for C*07:01 but a higher variability for C*06:02, C*04:01 and C*03:04 alleles were detected. The previously reported associations between HLA-C cell surface expression and -32 kb/-35 kb single nucleotide polymorphisms were not confirmed. Related and unrelated individuals sharing the same two A-B-C-DRB1 or B-C haplotypes show strikingly similar levels of HLA-C mRNA expression in each of the different haplotypic combinations tested. Altogether, our results suggest that HLA-C expression levels best correlate with the extended HLA haplotype rather than with the allotype or with polymorphisms in the 5'-region of the HLA-C locus.
National Reference Laboratory for Histocompatibility, Transplantation Immunology Unit, Department of Genetics and Laboratory Medicine, University Hospital, Geneva, Switzerland.
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F
Bettens
National Reference Laboratory for Histocompatibility, Transplantation Immunology Unit, Department of Genetics and Laboratory Medicine, University Hospital, Geneva, Switzerland.
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L
Brunet
National Reference Laboratory for Histocompatibility, Transplantation Immunology Unit, Department of Genetics and Laboratory Medicine, University Hospital, Geneva, Switzerland.
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JM
Tiercy
D000483:Alleles; D015870:Gene Expression; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger
D015236:HLA-C Antigens; D012333:RNA, Messenger