The Journal of Immunology, Vol 148, Issue 8 2572-2577, Copyright © 1992 by American Association of Immunologists

ARTICLES

cis-acting regulatory elements abrogate allele-specific HLA class I gene expression in healthy individuals

NM Lardy, RM Bakas, AR van der Horst, E van Twuyver, RE Bontrop and LP de Waal
Department of Transplantation Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.

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.

This article has been cited by other articles:

				Y. Watanabe, K. E. Magor, and P. Parham Exon 5 Encoding the Transmembrane Region of HLA-A Contains a Transitional Region for the Induction of Nonsense-Mediated mRNA Decay J. Immunol., December 15, 2001; 167(12): 6901 - 6911. [Abstract] [Full Text] [PDF]