Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexes.
Major histocompatibility complex (MHC) class I molecules associate with peptides derived from endogenously synthesized antigens. Cytotoxic T-lymphocytes can thus scan class I molecules and bound peptide on the surface of cells for foreign antigenic determinants. Recent evidence demonstrates that the products of trans-acting, non-class I genes in the class II region of the MHC are required in the class I antigen-processing pathway. There are genes (called HAM1 and HAM2 in the mouse) in this region that encode proteins postulated to be involved in the transport of peptide fragments into the endoplasmic reticulum for association with newly synthesized class I molecules. But, the mechanism by which such peptide fragments are produced remains a mystery. At least two genes encoding subunits of the low-molecular mass polypeptide (LMP) complex are tightly linked to the HAM1 and HAM2 genes. We show that the LMP complex is closely related to the proteasome (multicatalytic proteinase complex), an intracellular protein complex that has multiple proteolytic activities. We speculate that the LMP complex may have a role in MHC class I antigen processing, and therefore that the MHC contains a cluster of genes required for distinct functions in the antigen processing pathway.
Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0678.
M G
MG
Brown
J
J
Driscoll
J J
JJ
Monaco
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001704:Biopolymers; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000276:immunology*; D008285:Major Histocompatibility Complex; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011233:Precipitin Tests; D046988:Proteasome Endopeptidase Complex
D000941:Antigens; D001704:Biopolymers; D009097:Multienzyme Complexes; D010455:Peptides; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex