MHC-LINKED LOW-MOLECULAR-MASS POLYPEPTIDE SUBUNITS DEFINE DISTINCT SUBSETS OF PROTEASOMES - IMPLICATIONS FOR DIVERGENT FUNCTION AMONG DISTINCT PROTEASOME SUBSETS

Proteasomes are 650-kDa, multisubunit endopeptidases that might be inv olved in the MHC class I Ag processing pathway. We demonstrate the exi stence of multiple structurally distinct subsets of proteasomes. Disti nct forms of proteasomes share a hypothetical core to which unique sub units are added. One of these subsets, LMP2+ proteasome, contains the product of the MHC-linked Lmp-2 gene, and can be distinguished serolog ically and structurally from other proteasome subsets. The expression of LMP2+ and LMP2- proteasomes is variable among cell lines of differe nt tissue types, and their relative abundance and subunit composition are regulated by IFN-gamma. LMP2+ proteasomes comprise 0 to 74% of tot al cellular proteasomes. Both LMP2+ and LMP2- proteasomes are proteoly tically active. We suggest proteasome function might be regulated by s ubunit composition, and some, or all proteasome subsets, might partici pate in the production or delivery of peptides to MHC class I molecule s. Both LMP2+ and LMP2- subsets can be further subdivided on the basis of the presence or absence of other unique subunits. Implications of the existence of structurally distinct forms of proteasomes in differe nt tissue types is discussed.