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      Innate and Adaptive Immunity through Autophagy

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      1 , 1 ,
      Immunity
      Elsevier Inc.

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          Abstract

          The two main proteolytic machineries of eukaryotic cells, lysosomes and proteasomes, receive substrates by different routes. Polyubiquitination targets proteins for proteasomal degradation, whereas autophagy delivers intracellular material for lysosomal hydrolysis. The importance of autophagy for cell survival has long been appreciated, but more recently, its essential role in both innate and adaptive immunity has been characterized. Autophagy is now recognized to restrict viral infections and replication of intracellular bacteria and parasites. Additionally, this pathway delivers cytoplasmic antigens for MHC class II presentation to the adaptive immune system, which then in turn is able to regulate autophagy. At the same time, autophagy plays a role in the survival and the cell death of T cells. Thus, the immune system utilizes autophagic degradation of cytoplasmic material, to both restrict intracellular pathogens and regulate adaptive immunity.

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          Most cited references77

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          A ubiquitin-like system mediates protein lipidation.

          Autophagy is a dynamic membrane phenomenon for bulk protein degradation in the lysosome/vacuole. Apg8/Aut7 is an essential factor for autophagy in yeast. We previously found that the carboxy-terminal arginine of nascent Apg8 is removed by Apg4/Aut2 protease, leaving a glycine residue at the C terminus. Apg8 is then converted to a form (Apg8-X) that is tightly bound to the membrane. Here we report a new mode of protein lipidation. Apg8 is covalently conjugated to phosphatidylethanolamine through an amide bond between the C-terminal glycine and the amino group of phosphatidylethanolamine. This lipidation is mediated by a ubiquitination-like system. Apg8 is a ubiquitin-like protein that is activated by an E1 protein, Apg7 (refs 7, 8), and is transferred subsequently to the E2 enzymes Apg3/Aut1 (ref. 9). Apg7 activates two different ubiquitin-like proteins, Apg12 (ref. 10) and Apg8, and assigns them to specific E2 enzymes, Apg10 (ref. 11) and Apg3, respectively. These reactions are necessary for the formation of Apg8-phosphatidylethanolamine. This lipidation has an essential role in membrane dynamics during autophagy.
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            SYFPEITHI: database for MHC ligands and peptide motifs.

            The first version of the major histocompatibility complex (MHC) databank SYFPEITHI: database for MHC ligands and peptide motifs, is now available to the general public. It contains a collection of MHC class I and class II ligands and peptide motifs of humans and other species, such as apes, cattle, chicken, and mouse, for example, and is continuously updated. All motifs currently available are accessible as individual entries. Searches for MHC alleles, MHC motifs, natural ligands, T-cell epitopes, source proteins/organisms and references are possible. Hyperlinks to the EMBL and PubMed databases are included. In addition, ligand predictions are available for a number of MHC allelic products. The database content is restricted to published data only.
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              Functions of lysosomes.

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                Author and article information

                Contributors
                Journal
                Immunity
                Immunity
                Immunity
                Elsevier Inc.
                1074-7613
                1097-4180
                26 July 2007
                27 July 2007
                26 July 2007
                : 27
                : 1
                : 11-21
                Affiliations
                [1 ]Laboratory of Viral Immunobiology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
                Author notes
                []Corresponding author munzc@ 123456rockefeller.edu
                Article
                S1074-7613(07)00340-8
                10.1016/j.immuni.2007.07.004
                7118777
                17663981
                841a8ed2-a99f-4b6a-9853-99e2a04d54fc
                Copyright © 2007 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Immunology
                Immunology

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