Peptide antigen production by the proteasome: complexity provides efficiency.

Abstract Proteasomes have recently been shown to be central to the production of antigenic peptides that can bind to major histocompatibility complex class I molecules. Here, Marcus Groettrup and colleagues discuss the structural architecture of the proteasome and its proteolytic mechanisms with respect to the generation of antigenic peptides. They suggest that exchanges of proteolytic proteasome subunits and proteasome activators cooperate to optimize the production of antigens for cytotoxic T cells.

[1]  C. Slaughter,et al.  Primary structures of two homologous subunits of PA28, a γ‐interferon‐inducible protein activator of the 20S proteasome , 1995, FEBS letters.

[2]  A. Rivett,et al.  LMP2+ proteasomes are required for the presentation of specific antigens to cytotoxic T lymphocytes , 1995, Current Biology.

[3]  W. Baumeister,et al.  Existence of a molecular ruler in proteasomes suggested by analysis of degradation products , 1994, FEBS letters.

[4]  P. Kloetzel,et al.  LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12 , 1996, The Journal of experimental medicine.

[5]  J. Kleinz,et al.  Critical elements in proteasome assembly , 1994, Nature Structural Biology.

[6]  K. Tanaka,et al.  Molecular structure of 20S and 26S proteasomes. , 1993, Enzyme & protein.

[7]  K. Lilley,et al.  N‐Terminal sequence similarities between components of the multicatalytic proteinase complex , 1990, FEBS letters.

[8]  R Hegerl,et al.  Subunit stoichiometry and three‐dimensional arrangement in proteasomes from Thermoplasma acidophilum. , 1992, The EMBO journal.

[9]  J. Neefjes,et al.  Trimming of TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling , 1994, The Journal of experimental medicine.

[10]  P. Srivastava,et al.  Heat shock protein 70-associated peptides elicit specific cancer immunity , 1993, The Journal of experimental medicine.

[11]  M. Luscher,et al.  Peptide binding to class I MHC on living cells and quantitation of complexes required for CTL lysis , 1991, Nature.

[12]  H. Pircher,et al.  Strictly transporter of antigen presentation (TAP)-dependent presentation of an immunodominant cytotoxic T lymphocyte epitope in the signal sequence of a virus protein , 1995, The Journal of experimental medicine.

[13]  J. Monaco,et al.  Identification of MECL-1 (LMP-10) as the third IFN-gamma-inducible proteasome subunit. , 1996, Journal of immunology.

[14]  P. Kloetzel,et al.  20 S proteasomes are assembled via distinct precursor complexes. Processing of LMP2 and LMP7 proproteins takes place in 13-16 S preproteasome complexes. , 1994, Journal of molecular biology.

[15]  C. Dingwall.  Soluble factors and solid phases , 1992, Current Biology.

[16]  A. Goldberg,et al.  Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules , 1994, Cell.

[17]  R F Standaert,et al.  Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin , 1995, Science.

[18]  P. Cresswell,et al.  The protease inhibitor, N-acetyl-L-leucyl-L-leucyl-leucyl-L- norleucinal, decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum , 1996, The Journal of experimental medicine.

[19]  S. Tonegawa,et al.  Altered peptidase and viral-specific T cell response in LMP2 mutant mice. , 1994, Immunity.

[20]  A. Gruhler,et al.  PRE2, highly homologous to the human major histocompatibility complex-linked RING10 gene, codes for a yeast proteasome subunit necessary for chrymotryptic activity and degradation of ubiquitinated proteins. , 1993, The Journal of biological chemistry.

[21]  P. J. van den Elsen,et al.  Immunodominant mink cell focus-inducing murine leukemia virus (MuLV)-encoded CTL epitope, identified by its MHC class I-binding motif, explains MuLV-type specificity of MCF-directed cytotoxic T lymphocytes. , 1994, Journal of immunology.

[22]  C. Enenkel,et al.  PRE3, highly homologous to the human major histocompatibility complex‐linked LMP2 (RING12) gene, codes for a yeast proteasome subunit necessary for the peptidylglutamyl‐peptide hydrolyzing activity , 1994, FEBS letters.

[23]  P. Kloetzel,et al.  The Interferon-γ-inducible 11 S Regulator (PA28) and the LMP2/LMP7 Subunits Govern the Peptide Production by the 20 S Proteasome in Vitro(*) , 1995, The Journal of Biological Chemistry.

[24]  Clive A. Slaughter,et al.  Proteolytic Processing of Ovalbumin and β-galactosidase by the Proteasome to Yield Antigenic Peptides , 1994 .

[25]  Hans-Georg Rammensee,et al.  Cellular peptide composition governed by major histocompatibility complex class I molecules , 1990, Nature.

[26]  K. Tanaka,et al.  cDNA cloning and interferon gamma down-regulation of proteasomal subunits X and Y. , 1994, Science.

[27]  K. Rajewsky,et al.  MHC class I expression in mice lacking the proteasome subunit LMP-7. , 1994, Science.

[28]  J. Howard.  Supply and transport of peptides presented by class I MHC molecules. , 1995, Current opinion in immunology.

[29]  A. Goldberg,et al.  Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. , 1993, Nature.

[30]  M. Rechsteiner,et al.  Activation of the multicatalytic protease. The 11 S regulator and 20 S ATPase complexes contain distinct 30-kilodalton subunits. , 1994, The Journal of biological chemistry.

[31]  P. Kloetzel,et al.  A third interferon‐γ‐induced subunit exchange in the 20S proteasome , 1996, European journal of immunology.

[32]  K. Ferrell,et al.  Purification of an 11 S regulator of the multicatalytic protease. , 1992, The Journal of biological chemistry.

[33]  W Baumeister,et al.  Proteasome from Thermoplasma acidophilum: a threonine protease. , 1995, Science.

[34]  Dean R. Madden,et al.  The three-dimensional structure of HLA-B27 at 2.1 Å resolution suggests a general mechanism for tight peptide binding to MHC , 1992, Cell.

[35]  T. Elliott,et al.  Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport , 1995, European journal of immunology.

[36]  A. Goldberg,et al.  Rate of antigen degradation by the ubiquitin-proteasome pathway influences MHC class I presentation. , 1995, Journal of immunology.

[37]  H. Rammensee,et al.  Identification of naturally processed viral nonapeptides allows their quantification in infected cells and suggests an allele-specific T cell epitope forecast , 1991, The Journal of experimental medicine.

[38]  J. Neefjes,et al.  Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation , 1992, Nature.

[39]  H. von Boehmer,et al.  The thymus selects the useful, neglects the useless and destroys the harmful. , 1989, Immunology today.

[40]  M. Sakon,et al.  Proteasome and its novel endogeneous activator in human platelets. , 1991, Biochemical and biophysical research communications.

[41]  A. Johnsen,et al.  Human proteasome subunits from 2-dimensional gels identified by partial sequencing. , 1994, Biochemical and biophysical research communications.

[42]  C. Slaughter,et al.  PA28 activator protein forms regulatory caps on proteasome stacked rings. , 1994, Journal of molecular biology.

[43]  J. Trowsdale,et al.  Proteasome components with reciprocal expression to that of the MHC-encoded LMP proteins , 1994, Current Biology.

[44]  H. Ploegh,et al.  Generation, translocation, and presentation of MHC class I-restricted peptides. , 1995, Annual review of biochemistry.

[45]  Marcus Groettrup,et al.  Incorporation of major histocompatibility complex – encoded subunits LMP2 and LMP7 changes the quality of the 20S proteasome polypeptide processing products independent of interferon‐γ , 1995, European journal of immunology.

[46]  W. Baumeister,et al.  Conformational constraints in protein degradation by the 20S proteasome , 1995, Nature Structural Biology.

[47]  V. Engelhard.  Structure of peptides associated with MHC class I molecules. , 1994, Current opinion in immunology.

[48]  P M Kloetzel,et al.  Interferon gamma stimulation modulates the proteolytic activity and cleavage site preference of 20S mouse proteasomes , 1994, The Journal of experimental medicine.

[49]  R. Siliciano,et al.  Transporter-independent processing of HIV-1 envelope protein for recognition by CD8+ T cells , 1993, Nature.

[50]  E. Pamer,et al.  Efficiency of MHC class I antigen processing: a quantitative analysis. , 1994, Immunity.

[51]  J. Yewdell,et al.  Expression of a membrane protease enhances presentation of endogenous antigens to MHC class I-restricted T lymphocytes , 1992, Cell.

[52]  J. Yewdell,et al.  Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. , 1992, Advances in immunology.

[53]  M. Rechsteiner,et al.  Human lymphoblast and erythrocyte multicatalytic proteases: differential peptidase activities and responses to the 11S regulator , 1995, FEBS letters.

[54]  M. Rechsteiner,et al.  The multicatalytic and 26 S proteases. , 1993, The Journal of biological chemistry.

[55]  A. Goldberg,et al.  A role for the ubiquitin-dependent proteolytic pathway in MHC class l-restricted antigen presentation , 1993, Nature.

[56]  P. Cresswell,et al.  Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules , 1992, Nature.

[57]  K Eichmann,et al.  Contribution of proteasome-mediated proteolysis to the hierarchy of epitopes presented by major histocompatibility complex class I molecules. , 1995, Immunity.

[58]  W. Baumeister,et al.  The first characterization of a eubacterial proteasome: the 20S complex of Rhodococcus , 1995, Current Biology.

[59]  Hans-Georg Rammensee,et al.  A role for the proteasome regulator PA28α in antigen presentation , 1996, Nature.

[60]  T. Elliott,et al.  Processing of major histocompatibility class I-restricted antigens in the endoplasmic reticulum , 1995, The Journal of experimental medicine.

[61]  H. Rammensee,et al.  Peptides naturally presented by MHC class I molecules. , 1993, Annual review of immunology.

[62]  J. Yewdell,et al.  Trimming of antigenic peptides in an early secretory compartment , 1994, The Journal of experimental medicine.

[63]  R. Huber,et al.  Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution. , 1995, Science.

[64]  A. Kolstø,et al.  A tight cluster of five unrelated human genes on chromosome 16q22.1. , 1993, Human molecular genetics.

[65]  C. Slaughter,et al.  Identification, purification, and characterization of a protein activator (PA28) of the 20 S proteasome (macropain). , 1992, The Journal of biological chemistry.

[66]  D. Finley,et al.  MHC-linked LMP gene products specifically alter peptidase activities of the proteasome , 1993, Nature.

[67]  J. Yewdell,et al.  Presentation of endogenous and exogenous antigens is not affected by inactivation of E1 ubiquitin-activating enzyme in temperature-sensitive cell lines. , 1995, Journal of immunology.

[68]  J. Monaco,et al.  A molecular model of MHC class-I-restricted antigen processing. , 1992, Immunology today.

[69]  H. Rammensee,et al.  Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules , 1991, Nature.

[70]  K. Tanaka,et al.  Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma , 1996, The Journal of experimental medicine.

[71]  P. Cresswell,et al.  Processing and delivery of peptides presented by MHC class I molecules. , 1996, Current opinion in immunology.