Molecular basis for the quantitative differential expression of different HLA-A and -B antigens in cells

Abstract

Earlier studies have shown that different specific HLA-A and -B antigens are differentially expressed in cells. Their relative quantities are genetically predetermined and inherited according to Mendelian law (Human Immunol. 38:243, 1993). To investigate the molecular basis for the quantitative differential expression of HLA antigens, we studied the turnover of different HLA-A and -B antigens expressed in HLA-phenotyped EBV-transformed lymphoblastoid cell lines (LCLs) and found that different HLA-A and -B antigens in LCLs have the same stability. When the relative quantities of different HLA-A and -B proteins were correlated with the relative amounts of their mRNAs in ten LCLs, they were proportionally correlated, except for cell lines positive for HLA-A24 and-B7. Measurement of the relative quantities of HLA-A and -B mRNAs in seven LCLs before and after DRB treatment showed that different specific HLA-A and -B mRNAs in five LCLs have the same turnover rates. The HLA-A and -B mRNA stability in the other two LCLs is slightly different. These findings suggest that the quantitative differential expression of HLA-A and -B antigens is primarily determined by the rate of HLA gene transcription. Stability or translation rate of mRNA also may play a role in regulating the differential expression of certain phenotypes of HLA antigens. Nuclear run-on experiments are being conducted to further confirm these findings.