Negative regulation by HLA-DO of MHC class II-restricted antigen processing.
HLA-DM is a major histocompatibility complex (MHC) class II-like molecule that facilitates antigen processing by catalyzing the exchange of invariant chain-derived peptides (CLIP) from class II molecules for antigenic peptides. HLA-DO is a second class II-like molecule that physically associates with HLA-DM in B cells. HLA-DO was shown to block HLA-DM function. Purified HLA-DM-DO complexes could not promote peptide exchange in vitro. Expression of HLA-DO in a class II+ and DM+, DO- human T cell line caused the accumulation of class II-CLIP complexes, indicating that HLA-DO blocked DM function in vivo and suggesting that HLA-DO is an important modulator of class II-restricted antigen processing.
Denzin
L K
LK
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA.
Sant'Angelo
D B
DB
Hammond
C
C
Surman
M J
MJ
Cresswell
P
P
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D006681:HLA-D Antigens / Q000378:metabolism*; D015803:HLA-DR3 Antigen / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D000944:Antigens, Differentiation, B-Lymphocyte; C416186:H-2O antigen; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D015803:HLA-DR3 Antigen; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; C045084:invariant chain