Abstract
The antigen-specific activation of CD4-positive T helper cells depends on the recognition of a complex of MHC class II molecules and an antigen-derived peptide on the surface of antigen-presenting cells (APC). For most antigens generation of this MHC/peptide complex requires the uptake of the respective antigen by APC, followed by intracellular processing. The latter leads to suitable peptides of the antigen which are able to bind to MHC class ll-molecules. Subsequently the resulting complexes are transported to the cell surface. Evidence supporting this concept came mainly from the finding that agents such as chloroquine1, interfering with the function of endosomes and lysosomes, can block antigen presentation. The importance of proteolysis was demonstrated by the observation that certain preformed peptides do not require further processing and can also be presented by metabolically inactivated APC2. Nevertheless, the enzymes that are responsible for antigen processing are only known in few cases. Here we will describe the processing requirements for different protein antigens, all shown to need processing by APC prior to binding to MHC class II molecules: bovine insulin (Bl), its S-sulfonated chymotryptic A-chain fragment (BI-A1-14), porcine insulin (PI), human insulin (Hul), ovalbumin (OVA), and conalbumin (CA).
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References
H. K. Ziegler and E. R. Unanue. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells, Proc. NatlAcad. Sci. USA. 79: 175 (1982)
R. Shimonkevitz, J. Kappler, P. Marrack and H. Grey. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing, J. Exp. Med. 158: 303 (1983)
J. Puri and Y. Factorovich. Selective inhibition of antigen presentation to cloned T cells by protease inhibitors, J. Immunol. 141: 3313 (1988)
S. Diment. Different roles for thiol and aspartyl proteases in antigen presentation of ovalbumin, J. lmmunol. 145: 417 (1990)
G. Gradehandt, J. Hampl, D. Plachov, K. Reske and E. Rude. Processing requirements for the recognition of insulin fragments by murine T cells, Immunol. Rev. 106: 59 (1988)
G. Gradehandt, J. Hampl, S. Milbradt and E. Rude. Processing without proteolytic cleavage is required for recognition of insulin by T cells, Eur. J. lmmunol. 20: 2637 (1990)
L. Vidard, K. L. Rock and B. Benacerraf. The generation of immunogenic peptides can be selectively increased or decreased by proteolytic enzyme inhibitors, J. lmmunol. 147: 1786 (1991)
V. E. Reyes, S. Lu and R. E. Humphreys. Cathepsin B cleavage of li from class II MHC alpha and beta-chains, J. lmmunol. 146: 3877 (1991)
G. Gradehandt and E. Ruede. The endo/lysosomal protease cathepsin B is able to process conalbumin fragments for presentation to T cells, Immunology 74: 393 (1991)
K. Bennet, T. Levine, E. S. Ellis, R. J. Peanasky, I. M. Samloff, K. Kay and B. M. Chain. Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E, Eur. J. lmmunol. 22: 1519 (1992)
J. Hampl, G. Gradehandt, D. Plachov, H. G. Gattner, H. Kalbacher, W. Voelter, M. Meyer Delius and E. Rude. Presentation of insulin and insulin A chain peptides to mouse T cells: involvement of cysteine residues, Mol. lmmunol. 28: 479 (1991)
P. E. Jensen. Reduction of disulfide bonds during antigen processing: evidence from a thioldependent insulin determinant, J. Exp. Med. 174: 1121 (1991)
J. Hampl, G. Gradehandt, H. Kalbacher and E. Rüde. In vitro processing of insulin for recognition by murine T cells results in the generation of A-chains with free CysSH, J. lmmunol. 148: 2664 (1992)
D. S. Collins, E. R. Unanue and C. V. Harding. Reduction of disulfide bonds within lysosomes is a key step in antigen processing, J. lmmunol. 147: 4054 (1991)
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© 1993 Plenum Press, New York
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Gradehandt, G. et al. (1993). Requirements of Exogenous Protein Antigens for Presentation to CD4+ T lymphocytes By MHC Class II-Positive APC. In: Kamperdijk, E.W.A., Nieuwenhuis, P., Hoefsmit, E.C.M. (eds) Dendritic Cells in Fundamental and Clinical Immunology. Advances in Experimental Medicine and Biology, vol 329. Springer, New York, NY. https://doi.org/10.1007/978-1-4615-2930-9_4
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DOI: https://doi.org/10.1007/978-1-4615-2930-9_4
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