Expression of CD1c enhances human invariant NKT cell activation by α-GalCer. Cancer Immun 2013;13:9
Date
07/26/2013Pubmed ID
23885215Pubmed Central ID
PMC3721260Scopus ID
2-s2.0-84879033899 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
Invariant natural killer T (iNKT) cells are innate T lymphocytes that specifically recognize α-linked glycosphingolipids (α-GSLs) as antigens presented by CD1d molecules. Activating iNKT cells by administering α-GSLs improves disease outcomes in murine cancer models and, thus, there is great interest in the clinical potential of these lipids for treating human cancers. However, humans possess several other CD1 isoforms that are not present in mice and it is not clear whether these CD1 molecules, which also bind lipids, affect human iNKT cell responses. We demonstrate here that CD1c, which is co-expressed with CD1d on blood dendritic cells and on a fraction of B cells, is able to present α-galactosylceramide (α-GalCer) as a weak agonist to human iNKT cells, and that the presence of CD1c synergistically enhances α-GalCerdependent activation of iNKT cells by CD1d. Primary human B cells expressing CD1c induced stronger iNKT cell responses to α-GalCer than the CD1c- subset, and an antibody against CD1c inhibited iNKT cell cytokine secretion. These results suggest that therapeutic activation of human iNKT cells by α-GSLs will be driven preferentially by CD1c+ cell types. Thus, B cell neoplasias that co-express CD1c and CD1d may be particularly susceptible to α-GSL therapy, and cancer vaccines using α-GSLs as adjuvants may be most effective when presented by CD1c+ antigen-presenting cells.
Author List
Fox LM, Miksanek J, May NA, Scharf L, Lockridge JL, Veerapen N, Besra GS, Adams EJ, Hudson AW, Gumperz JEAuthor
Amy W. Hudson PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Antigens, CD1
Dendritic Cells
Galactosylceramides
Glycoproteins
HeLa Cells
Humans
Lymphocyte Activation
Mice
Models, Molecular
Molecular Sequence Data
Natural Killer T-Cells
Protein Binding
