Bikoff E K, Kenty G, Van Kaer L
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
J Immunol. 1998 Apr 1;160(7):3101-10.
Mutant mouse strains expressing either p31 or p41 Ii chain appear equally competent with respect to their class II functional activities including Ag presentation and CD4+ T cell development. To further explore possibly divergent roles provided by alternative Ii chain isoforms, we compare class II structure and function in double mutants also carrying a null allele at the H2-DM locus. As for DM mutants expressing wild-type Ii chain, Aalpha(b)Abeta(b) dimers present in DM-deficient mice expressing either Ii chain isoform appear equally occupied by class II-associated Ii chain-derived peptides (CLIP). Surprisingly, in functional assays, these novel mouse strains exhibit strikingly different phenotypes. Thus, DM-deficient mice expressing wild-type Ii chain or p31 alone are both severely compromised in their abilities to present peptides. In contrast, double mutants expressing the p41 isoform display markedly enhanced peptide-loading capabilities, approaching those observed for wild-type mice. The present data strengthen evidence for divergent class II presentation pathways and demonstrate for the first time that functionally distinct roles are mediated by alternatively spliced forms of the MHC class II-associated Ii chain in a physiologic setting.
表达p31或p41Ii链的突变小鼠品系在其包括抗原呈递和CD4+T细胞发育在内的II类功能活性方面表现出同等的能力。为了进一步探索不同的Ii链异构体可能发挥的不同作用，我们比较了在H2-DM位点也携带无效等位基因的双突变体中的II类结构和功能。对于表达野生型Ii链的DM突变体，在表达任何一种Ii链异构体的DM缺陷小鼠中存在的Aalpha(b)Abeta(b)二聚体似乎同样被II类相关的Ii链衍生肽（CLIP）占据。令人惊讶的是，在功能测定中，这些新型小鼠品系表现出截然不同的表型。因此，仅表达野生型Ii链或p31的DM缺陷小鼠在呈递肽的能力上均严重受损。相比之下，表达p41异构体的双突变体显示出明显增强的肽加载能力，接近野生型小鼠的水平。目前的数据加强了关于不同II类呈递途径的证据，并首次证明在生理环境中，功能不同的作用是由MHC II类相关Ii链的可变剪接形式介导的。
