Assembly and intracellular transport of HLA-DM and correction of the class II antigen-processing defect in T2 cells.
MHC class II molecules expressed in T2 cells fail to acquire a normal complement of endocytically generated peptides. The defect is repaired by introducing HLA-DMA and HLA-DMB cDNA expression vectors, determined by the restoration of SDS stability of class II alpha beta dimers, restoration of a normal conformation for HLA-DR3 as detected by a monoclonal antibody, and by a reduction in class II-associated invariant chain peptides. The intracellular distribution of class II and invariant chain molecules is also restored to that of wild-type cells. The HLA-DMA and HLA-DMB products appear to form a heterodimer that, although transported at least to the medial Golgi, is not expressed at the cell surface. These findings are consistent with HLA-DM functioning intracellularly to facilitate class II-restricted antigen processing.
Denzin
L K
LK
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Robbins
N F
NF
Carboy-Newcomb
C
C
Cresswell
P
P
D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry; D006681:HLA-D Antigens / Q000235:genetics / Q000502:physiology*; D015803:HLA-DR3 Antigen / Q000737:chemistry / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D006822:Hybrid Cells; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D011233:Precipitin Tests; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013997:Time Factors; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D015803:HLA-DR3 Antigen; D000949:Histocompatibility Antigens Class II; D009363:Neoplasm Proteins; C045084:invariant chain; D012967:Sodium Dodecyl Sulfate