title: Bcl-xL regulates CD1d-mediated antigen presentation to NKT cells by altering CD1d trafficking through the endocytic pathway.
abstract: NKT cells are a unique subset of T cells that recognize glycolipid Ags presented in the context of CD1d molecules. NKT cells mount strong antitumor responses and are a major focus in developing effective cancer immunotherapy. It is known that CD1d molecules are constantly internalized from the cell surface, recycled through the endocytic compartments, and re-expressed on the cell surface. However, little is known about the regulation of CD1d-mediated Ag processing and presentation in B cell lymphoma. Prosurvival factors of the Bcl-2 family, such as Bcl-xL, are often upregulated in B cell lymphomas and are intimately linked to sphingolipid metabolism, as well as the endocytic compartments. We hypothesized that Bcl-xL can regulate CD1d-mediated Ag presentation to NKT cells. We found that overexpression or induction of Bcl-xL led to increased Ag presentation to NKT cells. Conversely, the inhibition or knockdown of Bcl-xL led to decreased NKT cell activation. Furthermore, knockdown of Bcl-xL resulted in the loss of CD1d trafficking to lysosome-associated membrane protein 1(+) compartments. Rab7, a late endosomal protein, was upregulated and CD1d molecules accumulated in the Rab7(+) late endosomal compartment. These results demonstrate that Bcl-xL regulates CD1d-mediated Ag processing and presentation to NKT cells by altering the late endosomal compartment and changing the intracellular localization of CD1d.
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201.
authors: Priyanka B
authors: PB
authors: Subrahmanyam
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201.
authors: Gregory B
authors: GB
authors: Carey
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201 twebb@som.umaryland.edu.
authors: Tonya J
authors: TJ
authors: Webb
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004705:Endocytosis / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D021381:Protein Transport / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D051020:bcl-X Protein / Q000235:genetics / Q000276:immunology*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D000090802:rab7 GTP-Binding Proteins; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D055610:Antigens, CD1d; D051907:Lysosomal Membrane Proteins; D051020:bcl-X Protein; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; C494812:Bcl2l1 protein, mouse; C584692:CD1d antigen, mouse; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse