UvA - DARE ( Digital Academic Repository ) 5 ' Regulatory nucleotide sequence of an HLA - A * 0101 null allele

mWe have previously demonstrated an HLAA*0101null allele segregating in a family with the HLAB8, -Cw7, -DR3, -DR52, -DQ2 haplotype. In the present study the regulatory elements with known transcription enhancement activity of the silenced HLA-A*0101 allele were analyzed. In the enhancer B element, a T was substituted for a C at position – 106, whereas no other alterations were found in the adjacent 59 section of the HLA-A*0101null allele. This substitution was not seen in the enhancer B elements of the corresponding genes involved in normal HLA-A*0101 membrane expression. Comparison of enhancer B element sequences of classical functional major histocompatibility complex (MHC) class I alleles demonstrated a high degree of conservation. In contrast, many MHC class I pseudogenes showed mutation in their enhancer B boxes. These results may indicate that the single mutation detected in the enhancer B element plays a pivotal role in the abolishment of membrane expression of the HLA-A*0101null allele.