5' REGULATORY NUCLEOTIDE-SEQUENCE OF AN HLA-A-ASTERISK-0101NULL ALLELE

We have previously demonstrated an HLA0101null allele segregating in a family with the HLA-B8, -Cw7, -DR3, -DR52, -DQ2 haplotype. In the pr esent study the regulatory elements with known transcription enhanceme nt activity of the silenced HLA-A0101 allele were analyzed. In the en hancer B element, a T was substituted for a C at position -106, wherea s no other alterations were found in the adjacent 5' section of the HL A-A0101null allele. This substitution was not seen in the enhancer B elements of the corresponding genes involved in normal HLA-A0101 memb rane expression. Comparison of enhancer B element sequences of classic al functional major histocompatibility complex (MHC) class I alleles d emonstrated a high degree of conservation. In contrast, many MHC class I pseudogenes showed mutation in their enhancer B boxes. These result s may indicate that the single mutation detected in the enhancer B ele ment plays a pivotal role in the abolishment of membrane expression of the HLA-A0101null allele.