Synthesis and turnover of β₂-microglobulin in Ad12-transformed cells defective in assembly and transport of class I major histocompatibility complex molecules

In primary embryonal fibroblasts from transgenic mice expressing H-2 genes and a miniature swine class I transgene (PD1), transformation with the highly oncogenic Ad12 results in a reduction in peptide transporter and proteasome-associated (LMP2 and LMP7) gene expression, and suppression in transport and cell surface expression of all class I antigens. The selective suppression in transport of H-2 (but not of PD1) molecules in cells reconstituted for the expression of peptide transporter and LMP genes implied that an additional factor(s) is involved in the assembly of class I complexes. Here we show that the β₂m, H-2D^b, and H-2K^b genes are transcribed and translated in Ad12-transformed cells. However, unlike normal and E1Ad5-transformed cells, in which β₂m is either secreted unbound or bound to class I heavy chains, in Ad12-transformed cells significant amounts of β₂m are retained in the cell bound to the membrane, but free of class I heavy chains. This abnormal turnover of β₂m in the Ad12-transformed cells suggests the existence of a novel β₂m-binding molecule(s) that sequesters β₂m, and this process may provide a mechanism by which transformation with Ad12 may subvert class I complex formation.