Presentation of viral antigen by MHC class I molecules is dependent on a putative peptide transporter heterodimer.
Major histocompatibility complex (MHC) class I molecules present peptides derived from the endogenous protein pool to cytotoxic T lymphocytes, which can thus recognize intracellular antigen. This pathway may depend on a transporter (PSF1) to mediate entry of the cytosolic peptides into a pre-Golgi compartment where they bind to class I heavy chains and promote their stable assembly with beta 2-microglobulin. There is, however, only indirect support for this function of PSF1. Here we show that PSF1 is necessary for the efficient assembly of class I molecules and enables them to present a peptide epitope derived from endogenously synthesized viral antigen. Immunochemical and genetic data demonstrate that the PSF1 polypeptide is associated with a complementary transporter chain, which is polymorphic and is encoded by the PSF2 gene, which is closely linked to PSF1.
Spies
T
T
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Cerundolo
V
V
Colonna
M
M
Cresswell
P
P
Townsend
A
A
DeMars
R
R
D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D015789:HLA-A2 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D000956:Antigens, Viral; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I