Linkage of susceptibility to experimental allergic encephalomyelitis to the major histocompatibility locus in the rat

Abstract

Experimental allergic encephalomyelitis (EAE) was induced in rats of various genotypes by injection of 10 microg guinea pig basic protein in complete Freund's adjuvant containing 100 microg H(37) RV M. tuberculosis. Histologically verified EAE was present in 20/20 Lewis, 17/17 (Lewis x BN)F(1), 9/9 Lewis backcross, and 21/42 BN backcross rats. Among the BN backcross animals, 25/42 were determined to carry the major histocompatibility type characteristic of the Lewis strain and 21 of these had EAE. Separate groups of Lewis, BN, and (Lewis x BN)F(1) rats were immunized as described and skin tested on day 13 with 10 microg guinea pig basic protein and rat S basic protein. Animals of each genotype had Arthus and delayed skin reactivity to both antigens. These data are compatible with the hypothesis that susceptibility to EAE in rats is controlled by an autosomal dominant gene linked to the major histocompatibility locus. It is proposed that this is an immune response gene, designated Ir-EAE, which controls T cell reactivity directed against a highly encephalitogenic portion of the basic protein molecule.