Structure and expression of HLA-DQ ? and -DX ? genes: interallelic alternate splicing of the HLA-DQ ? gene and functional splicing of the HLA-DX ? gene using a retroviral vector

Abstract

The nucleotide sequences of the two closely related HLA-DQ _α and HLA-DX _α , genes have been determined. Exons coding for the signal peptide, α2 and transmembrane domains are 94–99% homologous, whereas the α1 exon and the promoter region have diverged as much as or more than introns and the 3′ untranslated region. The promoter regions of both genes contain two short sequences thought to be important for regulation of transcription by γ-interferon. Transfection studies established that the DQ _α and DQ _β genes encode the HLA-DQ antigen. Transcripts of varying length are produced from different alleles as the result of the use of alternate splice and polyadenylation signals at the 3′ end of the DQ _α gene. Thus typing at the DQ _α locus can be achieved by Northern blot analysis. No transcript of DX _α was detected in B lymphocytes. The DX _α gene was accurately spliced when introduced into a retroviral vector, suggesting that the lack of expression of DX _α is not due to aberrant splice signals.