Conservation of CD1 intracellular trafficking patterns between mammalian species.
Dendritic cells (DC) are potent APCs that sample Ags from the surrounding environment and present them to naive T cells using cell surface Ag-presenting molecules. The DC in both lymphoid and nonlymphoid tissues express high levels of CD1, a cell surface glycoprotein capable of presenting lipids and glycolipids to T cells. Distinct group 1 CD1 isoforms (CD1a, -b, -c) in man are known to traffic to different parts of the endocytic system where microbial Ags may be sampled. Guinea pigs are the only known rodent species that express the group 1 CD1 proteins. Therefore, we examined the expression and trafficking of guinea pig CD1 (gpCD1) isoforms on isolated DC. Confocal microscopy using mAbs specific for individual gpCD1 isoforms revealed differential trafficking of two distinct CD1b isoforms within DC. Colocalization of MHC class II was observed with the gpCD1b1 isoform, consistent with localization in the late endosomes of DC. In contrast, the gpCD1b3 isoform lacks an endosomal sorting motif and remains on the cell surface. Following incubation with Mycobacterium tuberculosis lipoarabinomannan, colocalization of endocytosed lipoarabinomannan with the gpCD1b1 isoform was observed but not with the gpCD1b3 isoform, which remained primarily on the cell surface. These data demonstrate that guinea pig DC express CD1 isoforms with unique trafficking patterns that recapitulate the patterns seen for human CD1 isoforms. This suggests evolutionary pressure for a conserved mechanism in mammals that allows CD1 to sample lipid Ags from various subcompartments of the endocytic system.
Dascher
Christopher C
CC
Division of Rheumatology, Immunology and Allergy, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. cdascher@rics.bwh.harvard.edu
Hiromatsu
Kenji
K
Xiong
Xiaowei
X
Sugita
Masahiko
M
Buhlmann
Janet E
JE
Dodge
Ingrid L
IL
Lee
Stella Y
SY
Roura-Mir
Carme
C
Watts
Gerald F
GF
Roy
Christopher J
CJ
Behar
Samuel M
SM
Clemens
Daniel L
DL
Porcelli
Steve A
SA
Brenner
Michael B
MB
D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000378:metabolism*; D002469:Cell Separation; D017124:Conserved Sequence / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000138:chemical synthesis; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018949:Antigens, CD1; C419394:CD1b antigen; D008024:Ligands; D008565:Membrane Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C084881:flt3 ligand protein