title: Cathepsin S regulates class II MHC processing in human CD4+ HLA-DR+ T cells.
abstract: Although it has long been known that human CD4(+) T cells can express functional class II MHC molecules, the role of lysosomal proteases in the T cell class II MHC processing and presentation pathway is unknown. Using CD4(+) T cell clones that constitutively express class II MHC, we determined that cathepsin S is necessary for invariant chain proteolysis in T cells. CD4(+)HLA-DR(+) T cells down-regulated cathepsin S expression and activity 18 h after activation, thereby ceasing nascent class II MHC product formation. This blockade resulted in the loss of the invariant chain fragment CLIP from the cell surface, suggesting that-like professional APC-CD4(+) HLA-DR(+) cells modulate self-Ag presentation as a consequence of activation. Furthermore, cathepsin S expression and activity, and concordantly cell surface CLIP expression, was reduced in HLA-DR(+) CD4(+) T cells as compared with B cells both in vitro and ex vivo.
authors: Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Cristina Maria
authors: CM
authors: Costantino
authors: Hidde L
authors: HL
authors: Ploegh
authors: David A
authors: DA
authors: Hafler
mesh_terms: D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001324:Autoantigens; D001402:B-Lymphocytes; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002403:Cathepsins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002999:Clone Cells; D015536:Down-Regulation; D006684:HLA-DR Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008247:Lysosomes / Q000201:enzymology; D010447:Peptide Hydrolases / Q000378:metabolism
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D002403:Cathepsins; D010447:Peptide Hydrolases; C028217:cathepsin S