Requirements of Exogenous Protein Antigens for Presentation to CD4+ T lymphocytes By MHC Class II-Positive APC
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).
KeywordsDisulfide Bond Antigen Processing Processing Requirement Porcine Insulin Protease Cathepsin
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- 4.S. Diment. Different roles for thiol and aspartyl proteases in antigen presentation of ovalbumin, J. lmmunol. 145: 417 (1990)Google Scholar
- 7.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)Google Scholar
- 8.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)Google Scholar
- 13.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)Google Scholar
- 14.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)Google Scholar