A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes.
Newly assembled major histocompatibility complex (MHC) class I molecules, together with the endoplasmic reticulum chaperone calreticulin, interact with the transporter associated with antigen processing (TAP) through a molecule called tapasin. The molecular cloning of tapasin revealed it to be a transmembrane glycoprotein encoded by an MHC-linked gene. It is a member of the immunoglobulin superfamily with a probable cytoplasmic endoplasmic reticulum retention signal. Up to four MHC class I-tapasin complexes were found to bind to each TAP molecule. Expression of tapasin in a negative mutant human cell line (220) restored class I-TAP association and normal class I cell surface expression. Tapasin expression also corrected the defective recognition of virus-infected 220 cells by class I-restricted cytotoxic T cells, establishing a critical functional role for tapasin in MHC class I-restricted antigen processing.
Ortmann
B
B
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA.
Copeman
J
J
Lehner
P J
PJ
Sadasivan
B
B
Herberg
J A
JA
Grandea
A G
AG
Riddell
S R
SR
Tampé
R
R
Spies
T
T
Trowsdale
J
J
Cresswell
P
P
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D017920:Antiporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037282:Calreticulin; D002460:Cell Line; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008040:Genetic Linkage; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008285:Major Histocompatibility Complex / Q000235:genetics; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D012261:Ribonucleoproteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic; D014407:Tumor Cells, Cultured
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D012261:Ribonucleoproteins; C073119:TAP1 protein, human; C107762:tapasin; C071692:TAP2 protein, human