The actin regulatory protein HS1 is required for antigen uptake and presentation by dendritic cells.
The hematopoietic actin regulatory protein hematopoietic lineage cell-specific protein 1 (HS1) is required for cell spreading and signaling in lymphocytes, but the scope of HS1 function in Ag presentation has not been addressed. We show that dendritic cells (DCs) from HS1(-/-) mice differentiate normally and display normal LPS-induced upregulation of surface markers and cytokines. Consistent with their normal expression of MHC and costimulatory molecules, HS1(-/-) DCs present OVA peptide efficiently to CD4(+) T cells. However, presentation of OVA protein is defective. Similarly, MHC class I-dependent presentation of VSV8 peptide to CD8(+) T cells occurs normally, but cross-presentation of GRP94/VSV8 complexes is defective. Analysis of Ag uptake pathways shows that HS1 is required for receptor-mediated endocytosis, but not for phagocytosis or macropinocytosis. HS1 interacts with dynamin 2, a protein involved in scission of endocytic vesicles. However, HS1(-/-) DCs showed decreased numbers of endocytic invaginations, whereas dynamin-inhibited cells showed accumulation of these endocytic intermediates. Taken together, these studies show that HS1 promotes an early step in the endocytic pathway that is required for efficient Ag presentation of exogenous Ag by DCs.
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yanping
Y
Huang
Chhanda
C
Biswas
Deborah A
DA
Klos Dehring
Uma
U
Sriram
Edward K
EK
Williamson
Shuixing
S
Li
Fiona
F
Clarke
Stefania
S
Gallucci
Yair
Y
Argon
Janis K
JK
Burkhardt
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015153:Blotting, Western; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000276:immunology*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010047:Ovalbumin / Q000276:immunology
C524015:hematopoietic lineage cell-specific protein 1, mouse; D016179:Granulocyte Colony-Stimulating Factor; D010047:Ovalbumin