Mechanisms for genetically predetermined differential quantitative expression of HLA-A and -B antigens

Previous studies showed that different HLA-A and -B antigens are differenti ally expressed in cells. Their relative quantities are generically predeter mined and inherited according to Mendelian laws. To investigate mechanisms responsible for this differential expression, a correlation study between t he relative quantities of different HLA-A and -B proteins and their mRNA le vels in eight different HLA-phenotyped lymphoblastoid cell lines (LCLs) wer e performed. The results show proportional correlation in all the studied c ell lines except those that are positive for HLA-A24. Study of the turnover of HLA antigens reveals that different HLA-A and -B antigens are proportio nally degraded. Measurement of the relative quantities of HLA-A and -B mRNA s in six LCLs before and after treatment with 5,6-dichloro-1 -beta-D-ribofu ranosylbenzimidazole (DRB), an inhibitor of RNA polymerase II, demonstrates that HLA-A and -B mRNAs are proportionally degraded except: slight differe nces in two LCLs. Measurement of che relative quantities of different HLA-A and -B pre-mRNAs in nuclei shows that they are not proportional to the rel ative quantities of their respective mature mRNAs in cytoplasm in four of s ix LCLs. These results indicate that combinations of different regulatory s teps which include gene transcription, pre-mRNA splicing and mRNA degradati on are involved in the genetically predetermined quantitative differential expression of HLA-A and -B antigens. Transcription of HLA genes and splicin g of HLA pre-mRNAs appear to be the dominant regulatory steps. Human Immuno logy 61, 799-807 (2000). (C) American Society for Histocompatibility and Im munogenetics, 2000. Published by Elsevier Science Inc.