Cathepsin S regulates class II MHC processing in human CD4+ HLA-DR+ T cells.
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.
Costantino
Cristina Maria
CM
Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Ploegh
Hidde L
HL
Hafler
David A
DA
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
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