The Effect of Copy Number on mRNA and Cell Surface Expression of an Aβ ^k Transgene

Abstract

Because allelic polymorphism of the class II antigens affects the immune response at several levels, we wanted to characterize the contribution of a particular chain or epitope in an in vivo system using transgenic mice. Initially, we introduced an Aβ^k genomic clone into [B10.S x SJL]F₂ (H-2^s/s) embryos and, from fourteen founders, have established twelve independent lines carrying from one to sixty-five copies of the transgene. The transgene was coexpressed with the endogenous allele in a tissue-specific manner, and Aβ^k mRNA expression correlated well with transgene copy number. Although the ratio of Aβ^k to Aβ^s expressed on the cell surface correlated well with the ratio of Aβ^k to Aβ^s mRNA, cell surface levels of the endogenous Aβ^s/Aα^s complex and total la were reduced in H-2^s/s mice overexpressing Aβ^k mRNA. However, extremely high levels of Aα^k/Aβ^k cell surface expression were observed in Aβ^k x Aα^k double transgenic mice, which implies that the excess mRNA is translated in the high copy number mice and that pairing of Aβ^k with Aα^s is permissive but inefficient. Initial immune response experiments reflected the variation in cell surface levels of Aβ^k (and total Ia) and suggested that expression of the Aα^s/Aβ^k heterodimer has some effect on the secondary antibody response to the I-A^k-restricted synthetic antigen (H,G)-A-L [(histidine, glutamic acid)-alanine-lysine; McDevitt and Chinitz 1969].