Sanderson S, Frauwirth K, Shastri N
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7217-21. doi: 10.1073/pnas.92.16.7217.
CD4+ T cells recognize major histocompatibility complex (MHC) class II-bound peptides that are primarily obtained from extracellular sources. Endogenously synthesized proteins that readily enter the MHC class I presentation pathway are generally excluded from the MHC class II presentation pathway. We show here that endogenously synthesized ovalbumin or hen egg lysozyme can be efficiently presented as peptide-MHC class II complexes when they are expressed as fusion proteins with the invariant chain (Ii). Similar to the wild-type Ii, the Ii-antigen fusion proteins were associated intracellularly with MHC molecules. Most efficient expression of endogenous peptide-MHC complex was obtained with fusion proteins that contained the endosomal targeting signal within the N-terminal cytoplasmic Ii residues but did not require the luminal residues of Ii that are known to bind MHC molecules. These results suggest that signals within the Ii can allow endogenously synthesized proteins to efficiently enter the MHC class II presentation pathway. They also suggest a strategy for identifying unknown antigens presented by MHC class II molecules.
CD4 + T细胞识别主要组织相容性复合体（MHC）II类结合的肽，这些肽主要来源于细胞外。容易进入MHC I类呈递途径的内源性合成蛋白通常被排除在MHC II类呈递途径之外。我们在此表明，当内源性合成的卵清蛋白或鸡卵溶菌酶与恒定链（Ii）作为融合蛋白表达时，它们可以有效地作为肽-MHC II类复合物呈递。与野生型Ii相似，Ii-抗原融合蛋白在细胞内与MHC分子相关联。内源性肽-MHC复合物的最有效表达是通过在N端细胞质Ii残基内包含内体靶向信号但不需要已知结合MHC分子的Ii腔残基的融合蛋白获得的。这些结果表明，Ii内的信号可以使内源性合成蛋白有效地进入MHC II类呈递途径。它们还提出了一种识别由MHC II类分子呈递的未知抗原的策略。
