title: The antigen presentation pathway in medullary thymic epithelial cells, but not that in cortical thymic epithelial cells, conforms to the endocytic pathway.
abstract: Murine medullary thymic epithelial cells (mTEC), but not cortical thymic epithelial cells (cTEC), are able to present a soluble antigen, ovalbumin, to helper T cells (Mizuochi, T. et al., J. Exp. Med. 1992. 175: 1601-1605). This functional difference between the mTEC and the cTEC is particularly important when we consider the thymic selection of the T cell repertoire. In the previous report, we proposed that mTEC and cTEC utilize two distinct antigen processing/presenting pathways (Kasai, M. et al., Eur. J. Immunol. 1996. 26: 2101-2107). In this report, we further confirmed this difference by analyzing (a) localization of MHC class II, H2-DM, and invariant chain (li) molecules, (b) the biochemical nature of MHC class II molecules, (c) the sensitivity of MHC class II alphabeta heterodimer formation to concanamycin A, a vacuolar H+-ATPase inhibitor, and (d) the subcellular distribution of MHC class II, H2-DM, and li molecules, in both TEC. Our results demonstrated that, in the mTEC, MHC class II, H2-DM and li molecules gain access to the endocytic pathway, where the luminal condition is acidic and thus li molecules are efficiently degraded and H2-DM molecules function well. In the cTEC, however, such molecules seemed to gain access to an alternative transport pathway, e.g. a secretory pathway, where the luminal condition is not fully acidic. These two distinct antigen processing pathways may account for the functional difference between mTEC and cTEC.
authors.affiliation: The Department of Bacterial and Blood Products, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kasai
authors.forename: E
authors.initials: E
authors.lastname: Kominami
authors.forename: T
authors.initials: T
authors.lastname: Mizuochi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D015415:Biomarkers; D003208:Concanavalin A / Q000494:pharmacology; D019281:Dimerization; D004705:Endocytosis; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006681:HLA-D Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008247:Lysosomes; D051379:Mice; D008969:Molecular Sequence Data; D013347:Subcellular Fractions; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D015415:Biomarkers; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D003208:Concanavalin A