The effect of excess β-chain synthesis on cell-surface expression of allele-mismatched class II heterodimers in vivo

We have recently described 12 lines of H-2^s/s mice carrying from 1 to 65 copies of an A_β^k transgene. The transgene was coexpressed with the endogenous allele, and A_β^k 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 A_β^k mRNA synthesis on I-A cell-surface expression in these mice. Crossing representatives from several lines of A_β^k mice to A_α^k transgenic mice demonstrated that the A_β^k mRNA was translated and expressed at high levels on the cell surface in association with A_α^k. In H-2^s/s (A_α^s/A_β^s) mice carrying >10 copies of the A_β^k transgene, excess A_β^k mRNA and protein synthesis did drive cell-surface expression of the less favored A_α^s/A_β^k heterodimers. However, the highest levels of A_β^k detected on the cell surface were only 50-70% of those observed in [B10.A(4R) x nontransgenic]F₁ controls. Maximum levels of A_α^s/A_β^k cell-surface expression were accompanied by a significant reduction in A_α^s/A_β^s 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 A_β^k transgene.