cis-acting regulatory elements abrogate allele-specific HLA class I gene expression in healthy individuals.
Pedigree analysis of a Dutch family revealed the presence of an HLA-A "blanc" allele segregating with the HLA-B8, -Cw7, -DR3, -DR52, -DQ2 haplotype. Precipitation studies, using selected mAb and sera directed against conserved epitopes of HLA class I products, failed to detect the expression of a corresponding HLA-A locus product. cDNA nucleotide sequence analysis of the HLA-A "blanc" specificity showed that the obtained sequence was identical to the authentic HLA-A1 gene revealing no mutations, deletions or recombinations that could influence translation or transport of a putative translation product to the cell surface. Mitogen stimulation, EBV transformation, or treatment with rIFN-gamma and rTNF-alpha did not induce HLA-A1 expression. Furthermore, cell-mediated lympholysis analysis revealed that individuals carrying the nonexpressed HLA-A1 gene could mount a strong anti-HLA-A1 T cell response, indicating that HLA-A1 was not expressed during T cell ontogeny. Therefore, this study describes for the first time the allele-specific down-regulation of the expression of a classical HLA class I gene segregating in healthy individuals.
Lardy
N M
NM
Department of Transplantation Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Bakas
R M
RM
van der Horst
A R
AR
van Twuyver
E
E
Bontrop
R E
RE
de Waal
L P
LP
D000483:Alleles; D001483:Base Sequence; D003001:Cloning, Molecular; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D015234:HLA-A Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D015854:Up-Regulation
D016207:Cytokines; D015234:HLA-A Antigens; D015395:Histocompatibility Antigens Class I