Abstract
Despite the observed coordinate expression of HLA-A and -B antigens in somatic tissues, there is growing evidence that the A and B class I genes are differentially regulated at the transcriptional level. Previous studies indicate that this may be related to locus-specific structural differences in certain enhancer elements. We have recently examined the 5' proximal regulatory regions of the A and B. homologs in the higher non-human primates and found pronounced differences between the locl. Sequence analysis shows the B-promoters are more homogeneous, whereas the A-locus promoters are divergent among the various species examined. The differences in A- and B- promoters is exemplified by the regulatory element referred to as the IFN-responsive element (IRE). While the B-locus IRE is conserved among all primates examined, the A-locus IRE are divergentand reveal different sequences in the human/chimpanzee, gorilla and orang-utan. In reporter gene bioassays, the B-locus IRE exhibited an enhancer activity in response to induction with IFN-β and IFN-γ. In contrast, all the variants of the A-locus IRE found in hominoid primates were unresponsive to IFN. One base substitution shared by all the primate IREs proved to be inactivating. These results provide a molecular basis of how duplicated gene loci encoding structurally and functionally similar antigen-presenting molecules may become differentially responsive to physiological stimulus.
Original language | English (US) |
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Pages (from-to) | 853-859 |
Number of pages | 7 |
Journal | International Immunology |
Volume | 7 |
Issue number | 5 |
DOIs | |
State | Published - May 1995 |
Keywords
- Class I MHC
- Evolution
- Gene expression
- IRE
- Promoter
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology