Journal of Experimental Medicine, Vol 182, 841-851, Copyright © 1995 by Rockefeller University Press

ARTICLES

Major histocompatibility complex class I presentation of peptides derived from soluble exogenous antigen by a subset of cells engaged in phagocytosis

C Reis e Sousa and RN Germain
Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-11892, USA.

Major histocompatibility complex (MHC) class I molecules generally present peptides derived from cytoplasmic proteins, but recent reports have suggested that macrophages (M phi) may be uniquely able to present exogenous antigens via these molecules, and that particle-associated antigens show a marked increase in the efficiency of such presentation. We confirm here that particle uptake by M phi permits exogenous ovaalbumin (OVA) to gain access to the endogenous class I processing pathway, an event that occurs rarely, if at all, in the absence of phagocytic stimuli. Presentation of soluble protein antigens by MHC class I molecules, however, is not limited to M phi, nor is direct coupling of antigen to the particle required. A variety of unconjugated particles promoted presentation of simultaneously offered soluble OVA to Kb-restricted T cells by both M phi and non-M phi antigen-presenting cells (APC), provided the latter could phagocytose the particles. Enhancement of presentation by phagocytic stimuli could not be explained by greater delivery of soluble antigen to endosomal compartments because such stimuli did not increase soluble tracer accumulation, nor did they improve presentation of OVA to an MHC class II-restricted T cell hybridoma. OVA presentation induced by cophagocytosis of particles and free antigen was nevertheless very inefficient in comparison to presentation of OVA peptide, and even modest responses required high concentrations of protein and particles. Furthermore, only a fraction of APC exposed to OVA and particles were lysed by anti-OVA cytotoxic T lymphocytes, despite virtually all cells showing OVA accumulation, particle uptake, and Kb expression. Titration experiments were most consistent with a model in which, by disrupting membrane integrity, phagocytic overload ("indigestion") allows escape of OVA into the cytosol of some APC, rather than with a model in which phagocytosis activates a novel antigen processing pathway that has evolved to permit class I loading of exogenous antigen. These data suggest caution in the development of vaccine strategies based on use of particle conjugates for elicitation of CD8+ T cell immunity, but, at the same time, may be relevant to understanding class I-restricted responses to some intracellular pathogens normally resident in membrane- bound vesicles.
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• Corr, M., von Damm, A., Lee, D. J., Tighe, H. (1999). In Vivo Priming by DNA Injection Occurs Predominantly by Antigen Transfer. J. Immunol. 163: 4721-4727 [Abstract] [Full Text]  
• Castellino, F., Boucher, P. E., Eichelberg, K., Mayhew, M., Rothman, J. E., Houghton, A. N., Germain, R. N. (1999). Receptor-mediated Uptake of Antigen/Heat Shock Protein Complexes Results in Major Histocompatibility Complex Class I Antigen Presentation via Two Distinct Processing Pathways. J. Exp. Med. 191: 1957-1964 [Abstract] [Full Text]  
• Lo, W.-F., Ong, H., Metcalf, E. S., Soloski, M. J. (1999). T Cell Responses to Gram-Negative Intracellular Bacterial Pathogens: A Role for CD8+ T Cells in Immunity to Salmonella Infection and the Involvement of MHC Class Ib Molecules. J. Immunol. 162: 5398-5406 [Abstract] [Full Text]  
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• Guermonprez, P., Ladant, D., Karimova, G., Ullmann, A., Leclerc, C. (1999). Direct Delivery of the Bordetella pertussis Adenylate Cyclase Toxin to the MHC Class I Antigen Presentation Pathway. J. Immunol. 162: 1910-1916 [Abstract] [Full Text]  
• Regnault, A., Lankar, D., Lacabanne, V., Rodriguez, A., Thery, C., Rescigno, M., Saito, T., Verbeek, S., Bonnerot, C., Ricciardi-Castagnoli, P., Amigorena, S. (1999). Fcgamma Receptor-mediated Induction of Dendritic Cell Maturation and Major Histocompatibility Complex Class I-restricted Antigen Presentation after Immune Complex Internalization. J. Exp. Med. 189: 371-380 [Abstract] [Full Text]  
• Wassenberg, J., Dezfulian, C, Nicchitta, C. (1999). Receptor mediated and fluid phase pathways for internalization of the ER Hsp90 chaperone GRP94 in murine macrophages. J. Cell Sci. 112: 2167-2175 [Abstract]  
• Shields, M. J., Kubota, R., Hodgson, W., Jacobson, S., Biddison, W. E., Ribaudo, R. K. (1998). The Effect of Human beta 2-Microglobulin on Major Histocompatibility Complex I Peptide Loading and the Engineering of a High Affinity Variant. IMPLICATIONS FOR PEPTIDE-BASED VACCINES. J. Biol. Chem. 273: 28010-28018 [Abstract] [Full Text]  
• Brewer, J. M., Tetley, L., Richmond, J., Liew, F. Y., Alexander, J. (1998). Lipid Vesicle Size Determines the Th1 or Th2 Response to Entrapped Antigen. J. Immunol. 161: 4000-4007 [Abstract] [Full Text]  
• Mark Tompkins, S., Kraft, J. R., Dao, C. T., Soloski, M. J., Jensen, P. E. (1998). Transporters Associated with Antigen Processing (TAP)-independent Presentation of Soluble Insulin to alpha /beta T Cells by the Class Ib Gene Product, Qa-1b. J. Exp. Med. 188: 961-971 [Abstract] [Full Text]  
• Yeh, K.-Y., McAdam, A. J., Pulaski, B. A., Shastri, N., Frelinger, J. G., Lord, E. M. (1998). IL-3 Enhances Both Presentation of Exogenous Particulate Antigen in Association with Class I Major Histocompatibility Antigen and Generation of Primary Tumor-Specific Cytolytic T Lymphocytes. J. Immunol. 160: 5773-5780 [Abstract] [Full Text]  
• Lewinsohn, D. M., Alderson, M. R., Briden, A. L., Riddell, S. R., Reed, S. G., Grabstein, K. H. (1998). Characterization of Human CD8+ T Cells Reactive with Mycobacterium tuberculosis-infected Antigen-presenting Cells. J. Exp. Med. 187: 1633-1640 [Abstract] [Full Text]  
• Toda, M., Martuza, R. L., Kojima, H., Rabkin, S. D. (1998). In Situ Cancer Vaccination: An IL-12 Defective Vector/Replication-Competent Herpes Simplex Virus Combination Induces Local and Systemic Antitumor Activity. J. Immunol. 160: 4457-4464 [Abstract] [Full Text]  
• Rescigno, M., Citterio, S., Thery, C., Rittig, M., Medaglini, D., Pozzi, G., Amigorena, S., Ricciardi-Castagnoli, P. (1998). Bacteria-induced neo-biosynthesis, stabilization, and surface expression of functional class I molecules in mouse dendritic cells. Proc. Natl. Acad. Sci. USA 95: 5229-5234 [Abstract] [Full Text]  
• Zhong, G., Sousa, C. R. e, Germain, R. N. (1997). Antigen-unspecific B Cells and Lymphoid Dendritic Cells Both Show Extensive Surface Expression of Processed Antigen-Major Histocompatibility Complex Class II Complexes after Soluble Protein Exposure In Vivo or In Vitro. J. Exp. Med. 186: 673-682 [Abstract] [Full Text]  
• Brossart, P., Bevan, M. J. (1997). Presentation of Exogenous Protein Antigens on Major Histocompatability Complex Class I Molecules by Dendritic Cells: Pathway of Presentation and Regulation by Cytokines. Blood 90: 1594-1599 [Abstract] [Full Text]  
• Bronte, V., Carroll, M. W., Goletz, T. J., Wang, M., Overwijk, W. W., Marincola, F., Rosenberg, S. A., Moss, B., Restifo, N. P. (1997). Antigen expression by dendritic cells correlates with the therapeutic effectiveness of a model recombinant poxvirus tumor vaccine. Proc. Natl. Acad. Sci. USA 94: 3183-3188 [Abstract] [Full Text]  
• Zhong, G., Romagnoli, P., Germain, R. N. (1997). Related Leucine-based Cytoplasmic Targeting Signals in Invariant Chain and Major Histocompatibility Complex Class II Molecules Control Endocytic Presentation of Distinct Determinants in a Single Protein. J. Exp. Med. 185: 429-438 [Abstract] [Full Text]  
• Gueguen, M., Long, E. O. (1996). Presentation of a cytosolic antigen by major histocompatibility complex class II molecules requires a long-lived form of the antigen. Proc. Natl. Acad. Sci. USA 93: 14692-14697 [Abstract] [Full Text]  

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