Delineation of a CD1d-restricted antigen presentation pathway associated with human and mouse intestinal epithelial cells.
OBJECTIVE
CD1d, a major histocompatibility complex (MHC) class I-related molecule that is responsible for the presentation of glycolipid antigens to subsets of natural killer T (NK-T) cells, is expressed by intestinal epithelial cells (IECs). However, CD1d-restricted antigen presentation has not yet been examined on IECs.


METHODS
A mouse intestinal epithelial cell line (MODE-K), a human epithelial cell line (T84), T84 cells transfected with CD1d and/or MHC class II, and freshly isolated human IECs were examined for their ability to present model glycolipid antigens to NK-T cells as defined by interleukin (IL)-2 or IL-4 secretion.


RESULTS
MODE-K and freshly isolated human IECs exhibited dose-dependent, CD1d-restricted presentation of the functional glycolipid antigen, alpha-galactosylceramide (alpha GalCer), to the mouse NK-T cell hybridoma, DN32.D3. The human IEC line, T84, mainly presented alpha GalCer when transfected with human CD1d. Presentation of alpha GalCer by CD1d-transfected T84 cells (T84d) to DN32.D3 cells was greater along the basal surface in comparison with the apical surface. Induction of the MHC class II antigen presentation machinery by cotransfecting T84d with the MHC class I transactivator (CIITA) did not alter this polarity of presentation. Neither MODE-K nor T84 cells transfected with CD1d, CD1d plus CIITA, or CD1d plus HLA-DR were able to present glycolipid antigens requiring intracellular processing. The MODE-K cell line could also present alpha GalCer to primary mouse NK-T cells.


CONCLUSIONS
CD1d is expressed functionally on IECs with a polarity of presentation (basal > apical) predicting a role in presentation of mucosal glycolipid antigens to local CD1d-restricted T cells.
Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Yvonne
Y
van de Wal
Nadia
N
Corazza
Matthieu
M
Allez
Lloyd F
LF
Mayer
Hideki
H
Iijima
Mark
M
Ryan
Steven
S
Cornwall
Dominique
D
Kaiserlian
Robert
R
Hershberg
Yasuhiko
Y
Koezuka
Sean P
SP
Colgan
Richard S
RS
Blumberg
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D016764:Cell Polarity / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008545:Melanoma; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human