THE EFFECT OF EXCESS BETA-CHAIN SYNTHESIS ON CELL-SURFACE EXPRESSION OF ALLELE-MISMATCHED CLASS-II HETERODIMERS INVIVO

We have recently described 12 lines of H-2s/s mice carrying from 1 to 65 copies of an Aβk transgene. The transgene was coexpressed with the endogenous allele, and Aβk mRNA expression correlated well with transgene copy number. Overexpression of the transgene was associated with a variety of defects, including a significant reduction in I-A cell-surface expression. In this paper, we assess the effect of increased levels of Aβk mRNA synthesis on I-A cell-surface expression in these mice. Crossing representatives from several lines of Aβk mice to Aαk transgenic mice demonstrated that the Aβk mRNA was translated and expressed at high levels on the cell surface in association with Aαk. In H-2s/s (Aαs/Aβs) mice carrying >10 copies of the Aβk transgene, excess Aβk mRNA and protein synthesis did drive cell-surface expression of the less favored Aαs/Aβk heterodimers. However, the highest levels of Aβk detected on the cell surface were only 50-70% of those observed in [B10.A(4R) x nontransgenic]F1 controls. Maximum levels of Aαs/Aβk cell-surface expression were accompanied by a significant reduction in Aαs/Aβs expression. Unpaired and improperly paired complexes were not detected intracellularly and appeared to be degraded quite rapidly. Thus, only a fraction of the chains competing for pairing reached the cell surface under conditions of asymmetric chain synthesis in these mice. This markedly reduced total Ia cell-surface levels in mice carrying >10 copies of the Aβk transgene.