Synthesis of HLA antigens from membrane-associated messenger RNA.

Proteins encoded by genes in the human major histocompatibility region, HLA, are present on the plasma membranes in the cells of most tissues. We have isolated messenger RNA (mRNA) from lymphoblastoid cells and studied its templating activity for HLA polypeptides by using an mRNA-dependent cell-free translation system and immunorecipitation with specific antisera. We estimate the sizes of the mRNA to be 1,700, 1,300, and 900 nucleotides for HLA-A, -B, and -C (HLA-ABC), HLA-DR, and beta 2-microglobulin, respectively. These sizes are consistent with our inability to detect larger polypeptide precursor for more than one HLA-ABC or HLA-DR antigen. Subcellular fractionation into cytosol and membrane fractions indicated that mRNA for the HLA-ABC and HLA-ABC and HLA-DR polypeptides was found predominantly in the membrane fraction. The beta 2-microglobulin mRNA appeared to be divided into roughly equal portions between both fractions. Nevertheless, we believe that in the cell, beta 2-microglobulin is synthesized in the rough endoplasmic reticulum, and that, because the protein is relatively small, the mRNA is released from the polyribosomes during the isolation procedure. We conclude that the properties of the HLA region and the beta 2-microglobulin mRNA are consistent with current models for the synthesis and membrane insertion of eukaryotic cell surface proteins. Our findings do not suggest the existence of multigenic precursor polypeptides for HLA antigens in contrast to those for several viral membrane glycoproteins.