Antigen Processing and Presentation the Role of the Endoplasmic Reticulum
The immune system has evolved to recognize and destroy pathogens. Invasion by extracellular microorganisms is mainly controlled by B lymphocytes which, using surface immunoglobulins (Ig) as receptors, recognize antigens in their native conformation either free in solution or on the surface of cells. Invasion by intracellular parasites is mainly controlled by cytotoxic T lymphocytes (CTL), which recognize foreign protein antigens on the surface of infected cells by a highly specific receptor and lyse the cells. Both CTL and B lymphocyte responses are specifically enhanced by lymphokines released by antigen-specific T helper cells. Unlike Ig, the T-cell receptor of both CTL and T helper cells does not recognize native proteins but it recognizes a binary complex formed by the association of peptides, derived from degradation of target proteins, with class I and class II molecules encoded in the major histocompatibility complex (MHC). Processing of target proteins occurs through two distinct pathways. Exogenous proteins are degraded in an endolysosome compartment, which intersects the biosynthetic pathway of MHC class II molecules (Neefjes et al., 1990). Thus, peptides derived from degradation of endocytosed proteins bind to MHC class II molecules. Newly synthesized proteins are degraded in the cytosol, and peptides generated from them are transported into the endoplasmic reticulum (ER) where they associate with MHC class I molecules. This review focuses on the latter pathway dealing with processing and presentation of intracellular proteins.
KeywordsMajor Histocompatibility Complex Major Histocompatibility Complex Class Intracellular Antigen Ethyl Methane Sulfonate Free Class
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- Anderson, K., Cresswell, P., Gammon, M., Hermes, J., Williamson, A., and Zweerink, H., 1991, Endogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class I-restricted cell-mediated lysis, J. Exp. Med. 174:489–492.PubMedCrossRefGoogle Scholar
- Braciale, T, Braciale, V., Winkler, M., Strynowski, I., Hood, L., Sabrook, J., and Gething, M., 1987, On the role of the transmembrane anchor sequence of influenza hemagglutinin in target cell recognition by class I MHC restricted, hemagglutinin-specific cytotoxic T lymphocytes, J. Exp. Med. 166:678–692.PubMedCrossRefGoogle Scholar
- Falk, K., Rötzschke, O., Deres, K., Metzger, I, Jung, G., and Rammensee, H.-G., 1991b, Identification of naturally processed viral nonapeptides allows their quantification in infected cells and suggests an allele-specific T cell epitope forecast, J. Exp. Med. 174:425–434.PubMedCrossRefGoogle Scholar
- Heinemeyer, W., Kleinschmidt, J., Sasidiwsky, J., Escher, C., and Wolf, D., 1991, Proteinase yscE, the yeast proteasome/multicatalytic-multifunctional Proteinase: Mutants unravel its function in stress induced proteolysis and uncover its necessity for cell survival, EMBO J. 10:555–567.PubMedGoogle Scholar
- Kelly, A., Powis, S., Kerr, L., Mockridge, I., Elliott, T., Bastin, J., Uchanska-Ziegler, B., Ziegler, A., Trowsdale, J., and Townsend, A., 1992, Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex, Nature 355:641–644.PubMedCrossRefGoogle Scholar
- Klein, J., 1986, Natural History of the Major Histocompatibility Complex, Wiley, New York.Google Scholar
- Ljunggren, H., Paabo, S., Cochet, M., Kling, G., Kourilsky, P., and Karre, K., 1989, Molecular analysis of H-2 deficit lymphoma lines. Distinct defects in biosynthesis and dissociation of MHC class I heavy chains and β-2m observed in cells with increased sensitivity to NK cell lysis, J. Immunol. 142:2911–2915.PubMedGoogle Scholar
- Ohlen, C., Bastin, J., Ljunggren, H.-G., Imreh, S., Klein, G., Townsend, A., and Karre, K., 1990, Restoration of H-2b expression and processing of endogenous antigens in the MHC class I pathway by fusion of a lymphoma mutant to L cells of the H-2k haplotype, Eur. J. Immunol. 20:1873–1876.PubMedCrossRefGoogle Scholar
- Pelham, H. R. B., 1991, Recycling of proteins between the endoplasmic reticulum and Golgi complex, Curr. Biol. 3:585–591.Google Scholar
- Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J. L., Drumm, M., Iannuzzi, M., Collins, F. S., and Tsui, L. C., 1989, Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA, Science 245:1066–1073.PubMedCrossRefGoogle Scholar
- Townsend, A., Bastin, J., Gould, K., Brownlee, G., Andrew, M., Coupar, D., Boyle, D., Chan, S., and Smith, G., 1988, Defective presentation to class I restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen, J. Exp. Med. 168:1211–1218.PubMedCrossRefGoogle Scholar