MHC-ENCODED PROTEASOME SUBUNIT-LMP2 AND SUBUNIT-LMP7 ARE NOT REQUIREDFOR EFFICIENT ANTIGEN PRESENTATION

LMP2 and LMP7 are proteins encoded by MHC genes that are tightly linke d to the genes encoding TAP, the transporter that conveys peptides fro m the cytosol to the endoplasmic reticulum for assembly with MHC class I molecules. LMP2 and LMP7 are subunits of a subset of proteasomes, l arge molecular assemblies with multi-proteolytic activities believed t o degrade damaged and unwanted cellular proteins. Like TAP and class I molecules themselves, expression of LMP genes is enhanced after expos ure of cells to IFN-gamma. These findings implicate LMP2 and LMP7 in t he 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 det erminants derived from viral proteins. For two determinants, the kinet ics of presentation are shown to be similar for LMP-expressing and -no nexpressing cells. We also demonstrate biochemically that peptide is n ot limiting in the assembly of class I molecules in LMP-nonexpressing cells. These findings provide additional evidence that LMP2 and LMP7 a re not required for efficient Ag presentation, and suggest that these proteins have either a more specialized role in the production of clas s I-associated peptides, or are not involved in the processing of prot eins for-association with class I molecules.