The purpose of this proposal is to comapre the expression of class II major histocopmatibility complex products by macrophages from mice that are resistant or susceptible to Mycobacterium bovis (strain BCG). The basis of this proposal stems from our observation that macrophages from mice that are resistant to BCG continuously express Ia antigens for up to 10 of in vitro culture. In contrast macrophages from mice that are susceptible to BCG transiently express Ia. Studies using congenic Balb/c and C.D2Ity-r mice strongly suggest that the Bcg-r phenotype influences the duration of I-A expression. Macrophages from the BCG resistant C.D2Ity-r mice continuously expressed I-A in vitro. We will explore the biology of induction of continuous I-A expression and determine whether the differences we have observed in BCG resistant and susceptible mice with regard to the expression of Ia lies at the level of the lymphoctye or macorphage. We will accomplish this by adoptively transferring cells between the two conginic strains. We explore the response of macrophages to different signals and the relationship of thses observations to disease resistance. We will also determine the mechanism of continued Ia expression after it is produced. Results in our laboratory together with those reported by others, strongly suggest that the association of invariant chain with Ia may acount for the continuous expression that we have observed. These studies usiong macorphages from Bcg-r and Bcg-s mice that express Ia differently, offer a unique opportunity to explore the functional significance of Ia-Ii association. Other studies will determine if continued expression is associated with membrane internalization and recycling of class II molecules.
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