Prigozy T I, Sieling P A, Clemens D, Stewart P L, Behar S M, Porcelli S A, Brenner M B, Modlin R L, Kronenberg M
Department of Microbiology and Immunology, University of California at Los Angeles 90095, USA.
Immunity. 1997 Feb;6(2):187-97. doi: 10.1016/s1074-7613(00)80425-2.
We have characterized the CD1b-mediated presentation pathway for the mycobacterial lipoglycan lipoarabinomannan (LAM) in monocyte-derived antigen-presenting cells. The macrophage mannose receptor (MR) was responsible for uptake of LAM. Antagonism of MR function inhibited both the internalization of LAM and the presentation of this antigen to LAM-reactive T cells. Intracellular MRs were most abundant in early endosomes, but they also were located in the compartment for MHC class II antigen loading (MIIC). Internalized LAM was transported to late endosomes, lysosomes, and MIICs. MRs colocalized with CD1b molecules, suggesting that the MR could deliver LAM to late endosomes for loading onto CD1b. LAM and CD1b colocalized in organelles that may be sites of lipoglycan antigen loading. This pathway links recognition of microbial antigens by a receptor of the innate immune system to the induction of adaptive T cell responses.
我们已经在单核细胞衍生的抗原呈递细胞中，对分枝杆菌脂多糖脂阿拉伯甘露聚糖（LAM）的CD1b介导的呈递途径进行了表征。巨噬细胞甘露糖受体（MR）负责LAM的摄取。MR功能的拮抗作用既抑制了LAM的内化，也抑制了该抗原向LAM反应性T细胞的呈递。细胞内MR在早期内体中最为丰富，但它们也位于MHC II类抗原加载区室（MIIC）中。内化的LAM被转运至晚期内体、溶酶体和MIIC。MR与CD1b分子共定位，表明MR可将LAM递送至晚期内体以加载到CD1b上。LAM和CD1b在可能是脂多糖抗原加载位点的细胞器中共定位。该途径将先天性免疫系统的受体对微生物抗原的识别与适应性T细胞反应的诱导联系起来。
