Analysis of differential HLA-DQB expression in autologous B cell lines.

Class II major histocompatibility complex genes are differentially expressed during cellular activation and differentiation, often in a locus-specific manner. We investigated the differential expression of the HLA-DQB gene, using B cell lines LAZ221 and LAZ388: LAZ221, derived from an early B cell leukemia, expresses HLA-DR but not HLA-DQ: LAZ388, the autologous Epstein-Barr virus-transformed B cell line, expresses both DR and DQ. Transfection experiments demonstrate differential function of class II gene upstream regulatory regions in the two lines, which correlates with differential class II gene expression.

Allele-specific DNA-protein interactions associated with the X-box regulatory region of the DQB1*0302 gene.

The X box is an essential transcriptional regulatory region for both constitutive and inducible expression of HLA-class II genes, and, while highly conserved among class II genes, both locus- and allele-specific polymorphisms exist. Using gel regardation analysis, we have analyzed the binding of B cell nuclear proteins to the X box regions of the DQB1*0302, *0301, and DRA genes and have identified two distinct X box binding complexes which differ for the diabetes-associated DQB1*0302 allele.

Locus- and allele-specific DNA-protein interactions in the HLA-DQB1 X box.

Expression of MHC class II genes is regulated by a complex series of protein-DNA interactions which lead to the initiation of transcription. Although the different MHC class II loci are generally coordinately expressed, important differences in expression can be seen among loci and among individual alleles. The major sites of transcriptional control in the human MHC consist of several highly conserved nucleotide sequence elements located upstream of each MHC class II gene.

Differential expression of related HLA class II DQ beta genes caused by nucleotide variation in transcriptional regulatory elements.

HLA class II genes comprise a large multigene family with intra- and interlocus variation in structure and expression. Within this family of related genes, the HLA-DX alpha and beta loci (HLA DQA2 and DQB2) are highly homologous to functional HLA-DQ loci (HLA DQA1 and DQB1) but are frequently termed pseudogenes because DX gene transcription has not been observed, even in cells expressing HLA-DQ. Analysis of upstream transcriptional regulatory elements for the DX beta and DQ beta genes identified a high degree of nucleotide homology, consistent with their derivation from a common ancestral class II gene.

Nonprogression of subclinical beta-cell dysfunction among first-degree relatives of IDDM patients. 5-yr follow-up of the Seattle Family Study.

It is unknown among first-degree relatives of individuals with insulin-dependent diabetes mellitus (IDDM) whether the disease process occurs in relatively few but always progresses to clinical IDDM or whether subclinical disease is more common but remains nonprogressive in many cases. Islet cell antibodies (ICAs) were found in 21 of 724 (2.9%) first-degree relatives during screening in the greater Seattle area between 1983 and 1988.