EVIDENCE FOR A SPECIFIC POSTTRANSCRIPTIONAL MECHANISM CONTROLLING THEEXPRESSION OF HLA-DQ, BUT NOT HLA-DR AND HLA-DP, MOLECULES

It is generally believed that the various MHC class II molecules are e xpressed coordinately in B cells. To investigate this aspect in more d etail, interspecies somatic cell hybrids were constructed between Raji or RJ 2.2.5 (a class II-negative derivative of Raji) human B cells an d M12.4.1 mouse B cells. In both types of hybrids, HLA-DR and -DP, but not -DQ, molecules were expressed at the cell surface. The specific l ack of expression of DQ Ags correlated with undetectability of newly s ynthesized DQ alpha beta heterodimers, as assessed by biosynthetic lab eling and immunoprecipitation with a variety of DQ-specific mAbs. Stud ies at the mRNA level showed that apparently normal DQ alpha and DQ be ta transcripts were present in the hybrids at levels comparable, if no t higher, with the levels of DR- and DP-specific transcripts. From the se results, we conclude that lack of appreciable amount of DQ molecule s in the hybrids is caused by a post-transcriptional block. To date, t hese findings represent a rather unique example of noncoordinate expre ssion of MHC class II Ags caused by distinct post-transcriptional mech anisms. These data may be relevant to a more correct interpretation of the functional role of the various MHC class II molecules, particular ly with regard to the well-known association of HLA-DQ with many autoi mmune diseases. Possible mechanisms at the basis of the distinct contr ol of expression within the MHC class II molecular pool are discussed.