MHC-encoded proteasome subunits LMP2 and LMP7 are not required for efficient antigen presentation.
LMP2 and LMP7 are proteins encoded by MHC genes that are tightly linked to the genes encoding TAP, the transporter that conveys peptides from the cytosol to the endoplasmic reticulum for assembly with MHC class I molecules. LMP2 and LMP7 are subunits of a subset of proteasomes, large molecular assemblies with multi-proteolytic activities believed to degrade damaged and unwanted cellular proteins. Like TAP and class I molecules themselves, expression of LMP genes is enhanced after exposure of cells to IFN-gamma. These findings implicate LMP2 and LMP7 in the cytosolic production of antigenic peptides. Doubts have been cast, however, on the role of LMP2 and LMP7 in Ag processing, because cells lacking these proteins possess class I molecules that contain peptides quantitatively and qualitatively indistinguishable from the peptides bound to class I molecules derived from normal cells. In this paper we show that cells lacking LMP2 and LMP7 present seven TAP-dependent determinants derived from viral proteins. For two determinants, the kinetics of presentation are shown to be similar for LMP-expressing and -nonexpressing cells. We also demonstrate biochemically that peptide is not limiting in the assembly of class I molecules in LMP-nonexpressing cells. These findings provide additional evidence that LMP2 and LMP7 are not required for efficient Ag presentation, and suggest that these proteins have either a more specialized role in the production of class I-associated peptides, or are not involved in the processing of proteins for association with class I molecules.
Yewdell
J
J
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Lapham
C
C
Bacik
I
I
Spies
T
T
Bennink
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D011506:Proteins; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex