Regulation of class I antigen expression in the rat

We have investigated the regulation of expression of class I transplantation antigens encoded by the A and E loci in the rat with regard to resting expression level, induction by interferon, and antigen turnover. Flow cytometric measurements showed that the expression of the A locus products is significantly greater than that of the E locus product. Comparisons among a number of haplotypes indicated that the expression of A locus products varies only marginally (+/- 20%) among strains and that expression of the E locus product is approximately one-fifth that of the A locus products. The influence of nonMHC genes on the expression of class I antigens was evaluated by comparing their expression in inbred and congenic strains: it was not significant in this system. Stimulation of lymphocytes with alpha or gamma interferon resulted in proportional increases in the expression of the antigens encoded by both the A and the E loci, and these increases in cell surface antigen expression were reflected in similar increases in the levels of class I mRNA and in the rate of antigen synthesis. Measurement of turnover kinetics showed that the turnover of the A locus antigens is substantially more rapid than that of the E locus antigen, and the difference in half-lives is 3-4-fold. The addition of a broadly reactive anti-class I monoclonal antibody resulted in significant dose-dependent inhibition of the proliferative response of lymph node lymphocytes stimulated with concanavalin A. The inhibition was maximal when the antibody was added during the early stages of activation.