title: Dendritic cells are the most efficient in presenting endogenous naturally processed self-epitopes to class II-restricted T cells.
abstract: Dendritic cells (DC) are potent APCs, able to induce efficiently primary T cell-mediated responses to foreign Ags. To assess the efficiency of DC, as compared with other APC types, in the in vivo presentation of self-Ags to CD4+ T cells, we analyzed processing and presentation to class II-restricted T cells of endogenous naturally processed self-epitopes constitutively expressed by mouse APC. Mouse beta 2-microglobulin (m beta 2-m) peptides corresponding to residues 26-39 and 24-36 are constitutively presented, in mice expressing m beta 2-m, by I-Ad and I-Ed molecules respectively, as demonstrated by activation of m beta 2-m-specific T cell hybridomas generated in BALB/c beta 2-m-deficient mice. These dominant, naturally processed self-epitopes of m beta 2-m are presented by APC from a variety of tissues, including the thymus. To analyze the relative efficiency of different APC populations in the presentation of self-beta 2-m, the ability of purified DC, macrophages, and large or small B cells to stimulate m beta 2-m-specific T cell hybridomas was tested. Naturally processed self-m beta 2-m epitopes are constitutively presented to T cells by any class II-positive APC tested, but with highest efficiency by splenic and thymic DC, followed by macrophages, large B cells, and small B cells. This hierarchy of self-beta 2-m presentation does not depend on differential processing capacity of these APC populations, and it correlates with expression of CTLA-4 ligands and ICAM-1 molecules, rather than with expression of class II molecules.
authors.affiliation: Roche Milano Richerche, Italy.
authors.forename: J C
authors.initials: JC
authors.lastname: Guéry
authors.forename: L
authors.initials: L
authors.lastname: Adorini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics*; D006825:Hybridomas; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013950:Thymus Gland / Q000166:cytology; D001613:beta 2-Microglobulin / Q000276:immunology
chemical_list: D001324:Autoantigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D001613:beta 2-Microglobulin