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 expressing only the p41 isoform of the conserved invariant (Ii) chain associated with MHC class II molecules. In contrast to mutants expressing only p31 Ii chain, a small proportion of A(alpha)b A(beta)b molecules produced by...

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Main Authors: Takaesu, N, Lower, J, Yelon, D, Robertson, E, Bikoff, E
Format: Journal article
Language:English
Published: 1997
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author Takaesu, N
Lower, J
Yelon, D
Robertson, E
Bikoff, E
author_facet Takaesu, N
Lower, J
Yelon, D
Robertson, E
Bikoff, E
author_sort Takaesu, N
collection OXFORD
description We used a "hit and run" gene targeting strategy to generate mice expressing only the p41 isoform of the conserved invariant (Ii) chain associated with MHC class II molecules. In contrast to mutants expressing only p31 Ii chain, a small proportion of A(alpha)b A(beta)b molecules produced by these animals have reduced mobilities in SDS-PAGE and appear incompletely processed. Nonetheless, class II surface expression, peptide occupancy, CD4+ T cell maturation, and proliferative responses toward intact protein Ags are efficiently reconstituted. Moreover, spleen cells exclusively expressing p41 or p31 alone display equivalent dose-response curves in Ag presentation assays. Similar conclusions were reached analyzing mutants expressing two independent MHC haplotypes. Overall, these results demonstrate that Ii chain functional activities as a class II-specific chaperone are largely shared by p31 and p41 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 useful 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.
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spelling oxford-uuid:447f8a52-2263-40e0-b893-5ab98ddef23f2022-03-26T15:01:50ZIn vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:447f8a52-2263-40e0-b893-5ab98ddef23fEnglishSymplectic Elements at Oxford1997Takaesu, NLower, JYelon, DRobertson, EBikoff, EWe used a "hit and run" gene targeting strategy to generate mice expressing only the p41 isoform of the conserved invariant (Ii) chain associated with MHC class II molecules. In contrast to mutants expressing only p31 Ii chain, a small proportion of A(alpha)b A(beta)b molecules produced by these animals have reduced mobilities in SDS-PAGE and appear incompletely processed. Nonetheless, class II surface expression, peptide occupancy, CD4+ T cell maturation, and proliferative responses toward intact protein Ags are efficiently reconstituted. Moreover, spleen cells exclusively expressing p41 or p31 alone display equivalent dose-response curves in Ag presentation assays. Similar conclusions were reached analyzing mutants expressing two independent MHC haplotypes. Overall, these results demonstrate that Ii chain functional activities as a class II-specific chaperone are largely shared by p31 and p41 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 useful 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.
spellingShingle Takaesu, N
Lower, J
Yelon, D
Robertson, E
Bikoff, E
In vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain.
title In vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain.
title_full In vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain.
title_fullStr In vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain.
title_full_unstemmed In vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain.
title_short In vivo functions mediated by the p41 isoform of the MHC class II-associated invariant chain.
title_sort in vivo functions mediated by the p41 isoform of the mhc class ii associated invariant chain
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