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.
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.
Department Biomedical Science & Technology, Institute of Biomedical Science & Technology (IBST), Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
Hyeong-Jwa
HJ
Choi
Woo-Sung
WS
Choi
Jin-Yeon
JY
Park
Miglena G
MG
Prabagar
Kyeong-Hyeon
KH
Kang
Se Jin
SJ
Jeon
Sang Gyu
SG
Park
Chan Young
CY
Shin
Young-Sun
YS
Kang
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology*; D001692:Biological Transport; D001710:Biotin / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D020566:Dendritic Cells, Follicular / Q000276:immunology; D003911:Dextrans / Q000276:immunology*; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000276:immunology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000276:immunology*; D042541:Intracellular Space / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000955:Antigens, T-Independent; D001710:Biotin; D015815:Cell Adhesion Molecules; D003911:Dextrans; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C000717248:Hspa5 protein, mouse