The Effect of Copy Number on mRNA and Cell Surface Expression of an Aβk Transgene
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 Aβk genomic clone into [B10.S x SJL]F2 (H-2s/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 Aβk mRNA expression correlated well with transgene copy number. Although the ratio of Aβk to Aβs expressed on the cell surface correlated well with the ratio of Aβk to Aβs mRNA, cell surface levels of the endogenous Aβs/Aαs complex and total la were reduced in H-2s/s mice overexpressing Aβk mRNA. However, extremely high levels of Aαk/Aβk cell surface expression were observed in Aβk x Aαk double transgenic mice, which implies that the excess mRNA is translated in the high copy number mice and that pairing of Aβk with Aαs is permissive but inefficient. Initial immune response experiments reflected the variation in cell surface levels of Aβk (and total Ia) and suggested that expression of the Aαs/Aβk heterodimer has some effect on the secondary antibody response to the I-Ak-restricted synthetic antigen (H,G)-A-L [(histidine, glutamic acid)-alanine-lysine; McDevitt and Chinitz 1969].
KeywordsToxicity Albumin Lysine Interferon Alanine
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