Rovere P, Forquet F, Zimmermann V S, Trucy J, Ricciardi-Castagnoli P, Davoust J
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Adv Exp Med Biol. 1997;417:195-201. doi: 10.1007/978-1-4757-9966-8_33.
We investigated in H-2k mice bearing a genetically disrupted invariant chain (Ii) gene, the MHC class II expression and antigen presentation ability of dendritic cells (DC) freshly purified from the spleen (SpDC) or derived from bone marrow precursors (BMDC) upon treatment with GM-CSF. In the absence of Ii, class II alpha/beta heterodimers are expressed on the DC membranes to a similar extent than in control mice, in contrast to splenic B cells. Class II molecules immunoprecipitated from the plasma membrane of Ii deficient DC are compact indicating that the dimers are stabilized by antigenic peptides. Furthermore DC from Ii mutant mice are able to present to CD4+ T lymphocytes, epitopes derived from the processing of the hen egg lysozyme (HEL) that normally require expression of the Ii molecule for presentation by B cells. All together, our results show that the antigen processing machinary of DC provides peptides that can reach class II molecules and stabilize their conformation in the absence of Ii mediated targeting of class II complexes.
我们在携带基因敲除恒定链(Ii)基因的H-2k小鼠中进行研究,观察了从脾脏新鲜纯化的树突状细胞(DC)(脾脏DC,SpDC)或由骨髓前体衍生的DC(骨髓DC,BMDC)在用粒细胞巨噬细胞集落刺激因子(GM-CSF)处理后,其MHC II类分子的表达及抗原呈递能力。与脾脏B细胞不同,在缺乏Ii的情况下,DC膜上II类α/β异二聚体的表达程度与对照小鼠相似。从Ii缺陷型DC的质膜免疫沉淀的II类分子结构紧密,表明二聚体由抗原肽稳定。此外,来自Ii突变小鼠的DC能够向CD4 + T淋巴细胞呈递源自鸡卵溶菌酶(HEL)加工过程的表位,而这些表位通常需要Ii分子表达才能由B细胞呈递。总之,我们的结果表明,在缺乏Ii介导的II类复合物靶向作用时,DC的抗原加工机制能提供可与II类分子结合并稳定其构象的肽段。