SIGN-R1, a C-type lectin, binds to Bip/GRP78 and this interaction mediates the regurgitation of T-cell-independent type 2 antigen dextran through the endoplasmic reticulum |
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Authors: | Hyeong-Jwa ChoiWoo-Sung Choi Jin-Yeon ParkMiglena G. Prabagar Kyeong-Hyeon KangSe Jin Jeon Sang Gyu ParkChan Young Shin Young-Sun Kang |
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Affiliation: | a Department Biomedical Science & Technology, Institute of Biomedical Science & Technology (IBST), Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea b College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea c Department of Biomedical Science, CHA university, 606-16, Yeoksam-dong, Kangnam-gu Seoul 135-081, Republic of Korea d Department of Pharmacology, School of Medicine, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea |
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Abstract: | Capsular polysaccharides of Streptococcus pneumoniae are representative T-cell-independent type 2 (TI-2) antigens, frequently causing serious infections in children, the elderly, and immunocompromised patients. However, the detailed mechanism of this immune escape by CPSs is poorly understood. To pursue this question, polysaccharide dextran, ligand of SIGN-R1 as well as an appropriate model of the immunogenicity of many TI-2 polysaccharide antigens was used. SIGN-R1 bound to binding immunoglobulin protein (BiP), a well-characterized endoplasmic reticulum (ER) chaperone, primarily in non-ER compartments. Interestingly, SIGN-R1+ macrophages in the MZ showed high expression of BiP, implying an important role of SIGN-R1 binding to BiP in vivo. To our surprise, dextran is rapidly transported into the ER and subsequently regurgitated out of cells in vitro or in vivo. BiP down-regulation in SIGN-R1 transfectant reduced the regurgitation of dextran, causing the accumulation of dextran in the ER.Therefore, these results demonstrated the first example to describe the intracellular trafficking and the regurgitation of TI-2 antigen dextran, suggesting the novel pathway of TI-2 antigen presentation to immune cells. |
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Keywords: | CPS, capsular polysaccharide of S. pneumoniae ER, endoplasmic reticulum FDCs, follicular dendritic cells area the MZ, the splenic marginal zone TI-2 antigens, T-cell-independent type 2 antigen |
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