PAProC: a prediction algorithm for proteasomal cleavages available on the WWW

Nussbaum, Alexander K.; Kuttler, Christina; Hadeler, K. P.; Rammensee, Hans‐Georg; Schild, Hansjörg

doi:10.1007/s002510100300

Cited by 182 publications

(154 citation statements)

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“…Today, some mathematical models (57, 74, 75) of proteasomal protein degradation have been performed, and meanwhile even programs are available that can predict the cleavage-pattern of a degraded protein (76) if the flanking 65 amino acids of the potential cleavage-site of the protein are known. How exactly the proteasomal degradation of a substrate is performed has to be investigated in detail, especially how the protein is feed stepwise into the inner chamber.…”

Section: The Proteasomementioning

confidence: 99%

The proteasome and its role in the degradation of oxidized proteins

2008

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SummaryThe generation of free radicals and the resulting oxidative modification of cell structures are omnipresent in mammalian cells. This includes the permanent oxidation of proteins leading to the disruption of the protein structure and an impaired functionality. In consequence, these oxidized proteins have to be removed in order to prevent serious metabolic disturbances. The most important cellular proteolytic system responsible for the removal of oxidized proteins is the proteasomal system. For normal functioning, the proteasomal system needs the coordinated interaction of numerous components. This review describes the fundamental functions of the 20S ''core'' proteasome, its regulators, and the roles of the proteasomal system beyond the removal of oxidized proteins in mammalian cells. IUBMBIUBMB Life, 60(11): 743-752, 2008

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Section: The Proteasomementioning

confidence: 99%

The proteasome and its role in the degradation of oxidized proteins

2008

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“…The latter efforts have led to the creation of algorithms that predict proteasome cleavage sites [90,91]. These algorithms have been combined with those for class I MHC peptide binding [92], and in some cases for TAP transport [93], to predict the peptide antigens most likely to be displayed.…”

Section: The Impact Of Antigen Processing Pathways On the Display Of mentioning

confidence: 99%

The contributions of mass spectrometry to understanding of immune recognition by T lymphocytes

Engelhard

2007

International Journal of Mass Spectrometry

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Over the last 15 years, the ability of mass spectrometry to analyze complex peptide mixtures and identify individual species has provided unprecedented insights into the repertoire of peptide antigens displayed by MHC molecules and recognized by T lymphocytes. These include: understanding the peptide binding specificity of MHC molecules; understanding of roles of different intracellular components of the antigen processing pathways in determining the peptide display; and identification of a large number of individual peptide antigens associated with infectious diseases, cancer, and transplant rejection that have provided the basis for new immunologically based therapies. This review will summarize the impact that the application of mass spectrometry has had on these advances, with particular attention to the contributions of Professor Donald Hunt and members of his laboratory, and point out the opportunities for future work. Keywordsantigen processing; post-translational modification; peptides; MHC molecules THE NATURE OF ANTIGEN RECOGNITION BY T LYMPHOCYTEST lymphocytes are a branch of the immune system concerned with recognition of antigens that are displayed on the surface of host cells. These antigens are produced through intracellular proteolytic mechanisms that create small peptides, which are then rescued and presented at the cell surface by adaptor proteins called MHC molecules [reviewed in [1-6]. The binding site of each MHC molecule enables it to bind to a wide range of different peptides, and results in the display of a repertoire of such antigens, each recognized by a distinct T lymphocyte. This "antigen processing and presentation" mechanism results in the display of peptides derived from the proteins of pathogens that have infected the cell or been taken up by endocytosis. Their recognition by T lymphocytes results in the development of an immune response, and results in clearance of the pathogen and infected cells from the body. However, antigen processing and presentation pathways operate constitutively on normal cellular proteins as well, resulting in the display of peptide antigens that can be distinguished on tumors and transplanted tissues. Some of these "self-peptides" are also involved in the development of T lymphocytes in the thymus, and their recognition also controls the balance between selftolerance and autoimmune disease. Correspondence: phone: 434-924-2423; fax: 434-924-1221; email: vhe@virginia.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In most individuals, molecules of each MHC class are expressed from 3 genetic loci that ...

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“…In this scenario the peptides derived from the allele A*0118N could potentially be recognized as minor histocompatibility Ags that could target for graft vs host disease. The presence of multiple cleavage sites by human proteasomes in the sequences of the mature protein of the A*0118N allele and the generation of peptides from the H chain of A*0118N by a web-based available program (16,17) indicated that peptides spanning residue 48 could be generated by the human proteasomes. Therefore, it is conceivable that one or more peptides derived from the intracellular protein A*0118N could be processed through the intracellular Ag processing pathway and be presented in the context of HLA class I and possibly by HLA class II molecules acting as minor histocompatibility Ags (28).…”

Section: Discussionmentioning

confidence: 99%

“…This analysis was performed utilizing the program PAProC (16,17). This program is a prediction tool for cleavages by human and yeast 20S proteasomes based on experimental cleavage data and is available online (ͳhttp://www.paproc.deʹ); the sequences of the HLA alleles were obtained from the IMGT/HLA Database (ͳhttp://www.ebi.ac.uk/imgt/hla/ʹ) (18).…”

Section: Prediction Of Proteosomal Cleavage Sites Of the Hla Alleles mentioning

confidence: 99%

Allorecognition of an HLA-A01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A0101 Allele

Almeciga

Wang

Zúñiga

et al. 2006

The Journal of Immunology

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We identified and characterized an HLA-A1 aberrant allele (A*0118N) resulting from a novel molecular mechanism; this allele was present in an unusually informative family with a near identical parental HLA haplotype (c d) differing only by one nucleotide substitution in one HLA-A allele, A*0118N, of the maternal HLA haplotype (c) and not of the paternal HLA haplotype (a). Although serologic HLA typing showed a “blank,” DNA molecular HLA typing detected a HLA-A*0118N allele. Sequence based typing identified the substitution of guanine by cytosine at the nucleotide position 215, which resulted in the replacement of arginine by proline at position 48 of the HLA-A1 H chain. The loss of surface protein expression was also found by FACS analysis. Isoelectric-focusing analysis detected a HLA-A H chain with a unique isoelectric-focusing pattern, which does not associate with the L chain (β2-microglobulin). These results suggest that the residue 48-containing interaction site on the α1 domain plays a critical role in the association between HLA class I H chain and β2-microglobulin. Functional studies showed that the T cells of the propositus (HLA haplotypes c d) carrying this null allele recognized its wild-type counterpart, HLA-A*010101, in her HLA-identical son that carries the HLA-A*0101 heterodimer. This is the first example of the generation of cytotoxic T cells in the absence of proliferation of CD4+ T cells (mixed lymphocyte culture) and the description of an aberrant allele, A*0118N, that may behave as a minor histocompatibility Ag, with implications in allorecognition by cytolytic T cells in solid organ and stem cell transplantation.

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PAProC: a prediction algorithm for proteasomal cleavages available on the WWW

Cited by 182 publications

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The proteasome and its role in the degradation of oxidized proteins

The proteasome and its role in the degradation of oxidized proteins

The contributions of mass spectrometry to understanding of immune recognition by T lymphocytes

Allorecognition of an HLA-A01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A0101 Allele

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PAProC: a prediction algorithm for proteasomal cleavages available on the WWW

Cited by 182 publications

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The proteasome and its role in the degradation of oxidized proteins

The proteasome and its role in the degradation of oxidized proteins

The contributions of mass spectrometry to understanding of immune recognition by T lymphocytes

Allorecognition of an HLA-A*01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A*0101 Allele

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Allorecognition of an HLA-A01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A0101 Allele