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Antigen Processing

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Macrophages and Related Cells

Part of the book series: Blood Cell Biochemistry ((BLBI,volume 5))

Abstract

The interrelationships between the macrophage and macrophage-related cells (e.g., the skin Langerhans cells, the veiled cells, the lymphoid dendritic cell, etc.) and the lymphocyte has long been a focus of attention for cellular immunologists. Of the many aspects of this interaction, one which has been studied most intensively over the past ten years is the role of the macrophage in T-lymphocyte activation. This interaction is itself made up of a multitude of molecular components, collectively known as antigen presentation. However, one of the most fundamental advances in our understanding of antigen presentation came with the realization that most antigens to which the immune system is exposed, be they bacteria, viruses, or simply purified proteins, must undergo changes, often radical ones, at a molecular level before they are recognized and hence signal a response to the T-lymphocyte compartment of the immune system. These changes, which occur predominantly within antigen-presenting cells, constitute antigen processing.

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References

  • Adorini, L., Appella, E., Doria, G., Cardinauz, F., and Nagy, Z. A., 1989, Competition for antigen presentation in living cells involves exchange of peptides bound by class II MHC molecules, Nature (London) 342: 800–803.

    Article  CAS  Google Scholar 

  • Aiba, S., and Katz, S. I., 1991, The ability of cultured Langerhans cells to process and present protein antigens is MHC-dependent, J. Immunol. 146: 2479–2487.

    PubMed  CAS  Google Scholar 

  • Bakke, O., and Dobberstein, B., 1990, MHC class II-associated invariant chain contains a sorting signal for endosomal compartments, Cell 63: 707–716.

    Article  PubMed  CAS  Google Scholar 

  • Bennett, K., Levine, T., Ellis, J. S., Peanasky, R. J., Samloff, I. M., Kay, J., and Chain, B. M., 1992, Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E, Eur J. Immunol. 22: 1519–1524.

    Article  PubMed  CAS  Google Scholar 

  • Besterman, J., Airhart, J. A., Woodworth, R. C., and Low, R. B., 1981, Exocytosis of pinocytosed fluid in cultured cells: Kinetic evidence for rapid turnover and compartmentation, J. Cell Biol. 91: 716–727.

    Article  PubMed  CAS  Google Scholar 

  • Bhardwaj, V., and Colston, M. J., 1988, The processing and presentation of mycobacterial antigens by human monocytes, Eur. J. Immunol. 18: 691–696.

    Article  PubMed  CAS  Google Scholar 

  • Blum, J. S., and Cresswell, P., 1988, Role for intracellular proteases in the processing and transport of class II HLA antigens, Proc. Natl. Acad. Sci. USA 85: 3975–3979.

    Article  PubMed  CAS  Google Scholar 

  • Brodsky, F. M., and Guagliardi, L., 1991, The cell biology of antigen processing and presentation, Annu. Rev. Immunol. 9: 707–744.

    Article  PubMed  CAS  Google Scholar 

  • Buus, S., and Werdelin, 0., 1986, A group specific inhibitor of lysosomal cysteine proteinases selectively inhibits both proteolytic degradation and presentation of the antigen DNP-poly-L-lysine by guinea pig accessory cells to T cells, J. Immunol. 136: 452–458.

    PubMed  CAS  Google Scholar 

  • Chain, B. M., and Kaye, P. M., 1986, Processing and presentation by dendritic cells—the role of the lysosome in antigen breakdown, in The Regulation of Gene Expression ( M. Feldmann and A. McMichael, eds.), pp. 207–219, Humana Press, Clifton, NJ.

    Chapter  Google Scholar 

  • Chain, B. M., Kaye, P. M., and Feldmann, M., 1986, The cellular pathway of antigen presentation: Biochemical and functional analysis of antigen processing in dendritic cells and macrophages, Immunology 58: 271–276.

    PubMed  CAS  Google Scholar 

  • Chain, B. M., Bou-Gharios, G., and Olsen, I., 1989, Endopeptidase activities associated with plasma membrane compartment of an antigen presenting B cell, Clin. Exp. Immunol. 75: 87–92.

    PubMed  CAS  Google Scholar 

  • Champion, B. R., Page, K. R., Parish, N., Rayner, D. C., Dawe, K., Biswas-Hughes, G., Cooke, A., Geysen, M., and Roitt, I. M., 1991, Identification of a thyroxine-containing self-epitope of thyroglobulin which triggers thyroid autoreactive T cells, J. Exp. Med. 174: 363–370.

    Article  PubMed  CAS  Google Scholar 

  • Davidson, H. W., and Watts, C., 1989, Epitope-directed processing of specific antigen by B lymphocytes, J. Cell Biol. 109: 85–92.

    Article  PubMed  CAS  Google Scholar 

  • Davidson, H. W., Reid, P. A., Lanzavecchia, A., and Watts, C., 1991, Processed antigen binds to newly synthesised MHC class II molecules in antigen specific B lymphocytes, Cell 67: 105–116.

    Article  PubMed  CAS  Google Scholar 

  • Demotz, S., Grey, H. M., Apella, E., and Sette, A., 1989, Characterisation of a naturally processed MHC class II-restricted T cell determinant of hen egg lysozyme, Nature (London) 342: 682–684.

    Article  CAS  Google Scholar 

  • Diment, S., 1990, Different roles for thiol and aspartyl proteases in antigen presentation of ovalbumin, J. Immunol. 145: 417–422.

    PubMed  CAS  Google Scholar 

  • Diment, S., Leech, M. S., and Stahl, P. D., 1988, Cathepsin D is membrane associated in macrophage endosomes. J. Biol. Chem. 263: 6901–6907.

    PubMed  CAS  Google Scholar 

  • Dunn, K. W., McGraw, T. E., and Maxfield, F. R., 1989, Iterative fractionation of recycling receptors from lysosomally destined ligands in an early sorting endosome, J. Cell BioL 109: 3303–3314.

    Article  PubMed  CAS  Google Scholar 

  • Eisenlohr, L. C., Gerhard, W., and Hackett, C. J., 1988, Individual class-II restricted antigenic determinants of the same protein exhibit distinct kinetics of appearance and persistence on antigen presentation cells, J. Immunol. 141: 2581–2584.

    PubMed  CAS  Google Scholar 

  • Forquet, F., Caln, V., Trescol-Biemont, M. C., Kanellopoulos, J., Mottez, E., Kourilsky, P., RabourdinCombe, C., and Gerlier, D., 1990, Generation of hen egg lysozyme-specific and major histocompatibility complex class I-restricted cytolytic T lymphocytes: Recognition of cytosolic and secreted antigen expressed by transfected cells, Eur. J. Immunol. 20: 2325–2332.

    Article  PubMed  CAS  Google Scholar 

  • Fox, B. S., Carbone, F. R., Germain, R. N., Paterson, Y., and Schwartz, R. H., 1988, Processing of minimal antigenic peptide alters its interaction with MHC molecules, Nature (London) 331: 538–540.

    Article  CAS  Google Scholar 

  • Gammon, G., Shastri, N., Cogswell, J., Wilbur, S., Sadegh-Nasseri, S., Krzych, U., Miller, A., and Sercarz, E., 1987, The choice of T cell epitopes utilized on a protein antigen depends on multiple factors distant from as well as at the determinant site, Immunol. Rev. 98: 53–73.

    Article  PubMed  CAS  Google Scholar 

  • Germain, R. N., and Hendrix, L. R., 1991, MHC class II structure, occupancy and surface expression determined by post-endoplasmic reticulum antigen binding, Nature (London) 353: 134–139.

    Article  CAS  Google Scholar 

  • Griffiths, G., and Gruenberg, J., 1991, The arguments for preexisting early and late endosomes, Trends Cell Biol. 1: 5–9.

    Article  PubMed  CAS  Google Scholar 

  • Gruenberg, J., Griffiths, G., and Howell, K. E., 1989, Characterisation of the early endosome and putative endocytic carrier vesicles in vivo and with an assay of vesicle fusion in vitro, J. Cell Biol. 108: 1301–1316.

    Article  PubMed  CAS  Google Scholar 

  • Guagliardi, L. E., Koppelman, B., Blum, J. S., Marks, M. S., Cresswell, P., and Brodsky, F. M., 1990, Co-localisation of molecules involved in antigen processing and presentation in an early endocytic compartment, Nature (London) 343: 133–139.

    Article  CAS  Google Scholar 

  • Guidos, C., Wong, M., and Lee, K.-C., 1984, A comparison of the stimulatory activities of lymphoid dendritic cells and macrophages in T proliferative responses to various antigens, J. Immunol. 133: 1179–1184.

    PubMed  CAS  Google Scholar 

  • Harding, C., and Unanue, E., 1989, Antigen processing, and intracellular Ia. Possible roles of endocytosis and protein synthesis in Ia function, J. Immunol. 142: 12–19.

    PubMed  CAS  Google Scholar 

  • Harding, C. V., Unanue, E. R., Slot, J. W., Schwartz, A. L., and Geuze, H. J., 1990, Functional and ultrastructural evidence for the intracellular formation of major histocompatibility complex class II-peptide complexes during antigen processing, Proc. Natl. Acad. Sci. USA 87: 5553–5557.

    Article  PubMed  CAS  Google Scholar 

  • Hopkins, C. R., Gibson, A., Shipman, M., and Miller, K., 1990, Movement of internalised ligand-receptor complexes along a continuous endosomal reticulum, Nature (London) 346: 335–339.

    Article  CAS  Google Scholar 

  • Jing, S., Spencer, T., Miller, K., Hopkins, C., and Trowbridge, I. S., 1990, Role for the human transferrin receptor cytoplasmic domain in endocytosis: Localisation of a specific signal sequence for internalisation, J. Cell Biol. 110: 283–294.

    Article  PubMed  CAS  Google Scholar 

  • Lanzavecchia, A., 1990, Receptor-mediated antigen uptake and its effects on antigen presentation to class II-restricted T cells, Annu. Rev. Immunol. 8: 773–793.

    Article  PubMed  CAS  Google Scholar 

  • Lechler, R. J., Norcross, M. A., and Germain, R. N., 1985, Quantitative studies of antigen presenting cell function using I-A expressing L cells, J. Immunol. 135: 2914–2922.

    PubMed  CAS  Google Scholar 

  • Lee, P., Matsueda, G., and Allen, P., 1988, T cell recognition of fibrinogen, J. Immunol. 140: 1063–1068.

    PubMed  CAS  Google Scholar 

  • Long, E. O., and Jacobson, S., 1989, Pathways of viral antigen processing and presentation to CTL: Defined by the mode of virus entry? Immunol. Today 10: 45–48.

    Article  PubMed  CAS  Google Scholar 

  • Lotteau, V., Teyton, L., Peleraux, A., Nilsson, T., Karlsson, L., Schmid, S., Quaranta, V., and Peterson, P. A., 1990, Intracellular transport of class II MHC molecules directed by invariant chain, Nature (London) 348: 600–605.

    Article  CAS  Google Scholar 

  • Madden, D. R., Gorga, J. C., Strominger, J. L., and Wiley, D. C., 1991, The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation, Nature (London) 353: 321–325.

    Article  CAS  Google Scholar 

  • Manca, F., Fenoglio, D., Kunkl, A., Cambiaggi, C., Sasso, M., and Celada, F., 1988, Differential activation of T cell clones stimulated by macrophages exposed to antigen complexed with monoclonal antibodies, J. Immunol. 140: 2893–2898.

    PubMed  CAS  Google Scholar 

  • Marcinkiewicz, J., Chain, B. M., Olszowska, E., Olsowski, S., and Zgliczynski, J. M., 1992, Enhancement of immunogenic properties of ovalbumin as a result of its chlorination, Int. J. Biochem., 23: 1393–1395.

    Article  Google Scholar 

  • Naquet, P., Ellis, J., Singh, B., Hodges, R. S., and Delovich, T. L., 1987, Processing and presentation of insulin. I. Analysis of immunogenic peptides and processing requirements for insulin A loop-specific T cells, J. Immunol. 139: 3955–3963.

    PubMed  CAS  Google Scholar 

  • Neefjes, J. J., Stollorz, V., Peters, P. J., Geuze, H. J., and Ploegh, H. L., 1990, The biosynthetic pathway of MHC class II but not class I molecules intersects the endocytic route, Cell 61: 171–183.

    Article  PubMed  CAS  Google Scholar 

  • Noort, J. M., Boon, J., Van der Drift, A. C. M., Wagenaar, J. P., Boots, A. M. H., and Boog, C. J. P., 1991, Antigen processing by endosomal proteases determines which sites of sperm-whale myoglobin are eventually recognised by T cells, Eur. J. Immunol. 21: 1989–1996.

    Article  PubMed  Google Scholar 

  • Parham, P., 1990, Antigen processing: Transporters of delight, Nature (London) 348: 674–675.

    Article  CAS  Google Scholar 

  • Peters, P. J., Neefjes, J. J., Oorschot, V., Ploegh, H. L., and Geuze, H. J., 1991, Segregation of MHC class II

    Google Scholar 

  • molecules from class I molecules in the Golgi complex for transport to lysosomal compartments, Nature (London) 349:669–676.

    Google Scholar 

  • Peterson, M., and Miller, J., 1990, Invariant chain influences the immunological recognition of MHC class II molecules, Nature (London) 345: 172–174.

    Article  CAS  Google Scholar 

  • Puri, J., and Factorovich, Y., 1988, Selective inhibition of antigen presentation to cloned cells by protease inhibitors, J. Immunol. 141: 3313–3317.

    PubMed  CAS  Google Scholar 

  • Puri, J., Lonai, P., and Friedman, V., 1986, Antigen–la interaction and the proteolytic processing of an antigen: The structure of the antigen determines its restriction to the A or E molecule of the MHC, Eur. J. Immunol. 16: 1093–1097.

    Article  CAS  Google Scholar 

  • Régnier-Vigouroux, A., El-Aych, M., Defendini, M.-L., Graniel, C., and Pierres, M., 1988, Processing by accessory cells for presentation to murine T cells ofapamin, a disulfide bonded 18 amino-acid peptide, J. Immunol. 140: 1069–1075.

    PubMed  Google Scholar 

  • Reid, P. A., and Watts, C., 1990, Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments, Nature (London) 346: 655–657.

    Article  CAS  Google Scholar 

  • Reyes, V. E., Lu, S., and Humphreys, R. E., 1991, Cathepsin B cleavage of Ii from class 11 MHC a and (3 chains, J. Immunol. 146: 3877–3880.

    PubMed  CAS  Google Scholar 

  • Robertson, M., 1991, Antigen processing—proteasomes in the pathway, Nature (London) 353:300–301. Roche, P. A., and Cresswell, P., 1990, Invariant chain association with HLA-DR molecules inhibits immunogenic binding, Nature (London) 345: 615–618.

    Google Scholar 

  • Romani, N. S., Koide, M., Crowley, M., Witmer-Pack, A. M., Livingstone, C., Fathman, C. G., Inaba, K., and Steinman, R. M., 1989, Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature epidermal Langerhans cells, J. Exp. Med. 169: 1169–1178.

    Article  PubMed  CAS  Google Scholar 

  • Roosnek, E., Demotz, S., Corradin, G., and Lanzavecchia, A., 1988, Kinetics of MHC-antigen complex formation on antigen presenting cells, J. Immunol. 140: 4079–4082.

    PubMed  CAS  Google Scholar 

  • Rötzschke, O., Falk, K., Waliny, H.-J., Faath, S., and Rammensee, H.-G., 1990, Characterization of naturally occurring minor histocompatibility peptides including H-4 and H-Y, Science 249: 283–287.

    Article  PubMed  Google Scholar 

  • Rudensky, A. Y., Preston-Hurlburt, P., Hong, S.-C., Barlow, A., and Janeway, C. A., Jr., 1991, Sequence analysis of peptides bound to MHC class II molecules, Nature (London) 353: 622–627.

    Article  CAS  Google Scholar 

  • Shaw, M.-A., and Chain, B. M., 1989, A cell-free model system for the study of antigen processing, Int. Immunol. 1: 619–623.

    Article  PubMed  CAS  Google Scholar 

  • Steinman, R. M., 1991, The dendritic cell system and its role in immunogenicity, Annu. Rev. Immunol. 9: 271–296.

    Article  PubMed  CAS  Google Scholar 

  • Streicher, H. Z., Berkower, I. J., Busch, M., Gurd, F. R. N., and Berzofsky, J. A., 1984, Antigen conformation determined processing requirements for T cell activation, Proc. Natl. Acad. Sci. USA 81: 6831–6835.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, H., Cease, K. B., and Berzofsky, J. A., 1989, Identification of proteases that process distinct epitopes on the same protein, J. Immunol. 142: 2221–2229.

    PubMed  CAS  Google Scholar 

  • Ukkonen, P., Lewis, V., Marsh, M., Helenius, A., and Mellman, I., 1985, Transport of macrophage Fc receptor and Fc receptor-bound ligands to lysosomes, J. Exp. Med. 163: 952–971.

    Article  Google Scholar 

  • Vanbuskirk, A., Crump, B. L., Margiolash, E., and Pierce, S., 1989, A peptide binding protein having a role in antigen presentation is a member of the HSP70 heat shock family, J. Exp. Med. 170: 1799–1809.

    Article  PubMed  CAS  Google Scholar 

  • Yewdell, J. W., and Bennink, J. R., 1990, The binary logic of antigen processing and presentation to T cells, Cell 62: 203–206.

    Article  PubMed  CAS  Google Scholar 

  • Yoshikawa, M., Watanabe, M., and Hozumi, N., 1987, Analysis of proteolytic processing during specific antigen presentation, Cell. Immunol. 110: 431–435.

    Article  PubMed  CAS  Google Scholar 

  • Ziegler, H. K., and Unanue, E. R., 1982, Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells, Proc. Natl. Acad. Sci. USA 79: 175–178.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Biology, University College London, London, WC1E 6BT, UK

    Benjamin M. Chain & Timothy P. Levine

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  1. Benjamin M. Chain
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  1. Imperial Cancer Research Fund Haemopoiesis Research Group, Department of Haematology, St. Bartholomew’s Hospital Medical College, EC1A 7BE, London, UK

    Michael A. Horton

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Chain, B.M., Levine, T.P. (1993). Antigen Processing. In: Horton, M.A. (eds) Macrophages and Related Cells. Blood Cell Biochemistry, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9534-9_6

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  • DOI: https://doi.org/10.1007/978-1-4757-9534-9_6

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