title: 5' and 3' untranslated regions contribute to the differential expression of specific HLA-A alleles.
abstract: In hematopoietic stem cell transplantation (HSCT), when no HLA full-matched donor is available, alternative donors could include one HLA-mismatched donor. Recently, the low expressed HLA-C alleles have been identified as permissive mismatches for the best donor choice. Concerning HLA-A, the degree of variability of expression is poorly understood. Here, we evaluated HLA-A expression in healthy individuals carrying HLA-A*02 allele in different genotypes using flow cytometry and allele-specific quantitative RT-PCR. While an interindividual variability of HLA-A*02 cell surface expression, not due to the allele associated, was observed, no difference of the mRNA expression level was shown, suggesting the involvement of the posttranscriptional regulation. The results of qRT-PCR analyses exhibit a differential expression of HLA-A alleles with HLA-A*02 as the strongest expressed allele independently of the second allele. The associated non-HLA-A*02 alleles were differentially expressed, particularly the HLA-A*31 and HLA-A*33 alleles (strong expression) and the HLA-A*29 (low expression). The presence of specific polymorphisms in the 5' and 3' untranslated regions of the HLA-A*31 and HLA-A*33 alleles could contribute to this high level of expression. As previously described for HLA-C, low-expressed HLA-A alleles, such as HLA-A*29, could be considered as a permissive mismatch, although this needs to be confirmed by clinical studies.
authors.affiliation: Department of Immunology, CHRU de Montpellier, University Hospital Saint-Eloi, Montpellier, France.|Faculté de Médecine, University of Montpellier, Montpellier, France.|INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France.
authors.forename: Céline
authors.initials: C
authors.lastname: René
authors.affiliation: Department of Immunology, CHRU de Montpellier, University Hospital Saint-Eloi, Montpellier, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lozano
authors.affiliation: INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France.|Institute for Regenerative Medicine and Biotherapy (IRMB), CHRU Montpellier, Montpellier, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Villalba
authors.affiliation: Department of Immunology, CHRU de Montpellier, University Hospital Saint-Eloi, Montpellier, France.|Faculté de Médecine, University of Montpellier, Montpellier, France.|INSERM U1194, IRCM University of Montpellier, Montpellier, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eliaou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D020121:5' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D015234:HLA-A Antigens; D015236:HLA-C Antigens; D012333:RNA, Messenger
keywords: Allele; Expression; HLA; Hematopoietic stem cell transplantation; Polymorphism