IN-VIVO FUNCTIONS MEDIATED BY THE P41 ISOFORM OF THE MHC CLASS II-ASSOCIATED INVARIANT CHAIN

We used a ''hit and run'' gene targeting strategy to generate mice exp ressing only the p41 isoform of the conserved invariant (Ii) chain ass ociated with MHC class II molecules, In contrast to mutants expressing only p31 Ii chain, a small proportion of A alpha(b)A beta(b) molecule s produced by these animals have reduced mobilities in SDS-PACE and ap pear incompletely processed, Nonetheless, class II surface expression, peptide occupancy, CD4(+) T cell maturation, and proliferative respon ses toward intact protein Ags are efficiently reconstituted, Moreover, spleen cells exclusively expressing p41 or p31 alone display equivale nt dose-response curves in Ag presentation assays, Similar conclusions were reached analyzing mutants expressing two independent MHC haploty pes, Overall, these results demonstrate that Ii chain functional activ ities as a class II-specific chaperone are largely shared by p31 and p 41 isoforms in the intact animal, Mutant mouse strains producing only p31 or p41 under control of endogenous regulatory elements responsible for constitutive and inducible Ii chain expression should prove usefu l for dissecting the contributions of these isoforms to diverse CD4(+) T cell responses in vivo, such as those responsible for Ab production , inflammatory responses, autoimmune diseases, and protection against infectious agents.