title: Human duodenal epithelial cells constitutively express molecular components of antigen presentation but not costimulatory molecules.
abstract: Constitutive expression of major histocompatibility complex (MHC) class II molecules by duodenal epithelial cells (EC) suggests that they can present antigen to CD4(+) T cells. However, other molecular components including invariant chain (Ii), HLA-DM, and costimulatory molecules CD80, CD86 and CD40, are required for efficient T-cell activation. We have investigated whether normal human duodenal EC possess these molecules and whether they can mediate MHC class II antigen presentation. EC were isolated from duodenal biopsies from patients in whom pathology was excluded. Freshly-isolated duodenal EC did not stimulate autologous T-cell proliferation against purified protein derivative of tuberculin. Flow cytometry and immunoblot analysis revealed that duodenal EC constitutively express HLA-DR, Ii, and HLA-DM. Surface MHC class II associated invariant chain peptide (CLIP) was not detectable, suggesting that HLA-DM functions normally in CLIP removal. Duodenal EC expressed SDS-stable HLA-DR alphabeta heterodimers, indicating that peptide binding had occurred. Surface expression of CD80, CD86 or CD40 was not detected although mRNA for these costimulatory molecules was present in all samples. These results suggest that nondiseased human duodenal EC can process and present antigen by the MHC class II pathway, but that they may induce anergy, rather than activation, of local T cells.
authors.affiliation: Education and Research Centre, St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Brendan
authors.initials: B
authors.lastname: Byrne
authors.forename: Laura
authors.initials: L
authors.lastname: Madrigal-Estebas
authors.forename: Alice
authors.initials: A
authors.lastname: McEvoy
authors.forename: Janet
authors.initials: J
authors.lastname: Carton
authors.forename: Derek G
authors.initials: DG
authors.lastname: Doherty
authors.forename: Alex
authors.initials: A
authors.lastname: Whelan
authors.forename: Conleth
authors.initials: C
authors.lastname: Feighery
authors.forename: Diarmuid P
authors.initials: DP
authors.lastname: O'Donoghue
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis / Q000235:genetics; D004386:Duodenum / Q000276:immunology*; D006681:HLA-D Antigens / Q000032:analysis / Q000235:genetics; D006684:HLA-DR Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C045084:invariant chain