Catheptic processing of protein antigens: enzymic and molecular aspects.
Processing of most exogenous protein antigens involves restricted intracellular proteolysis to yield fragments that may be bound specifically by MHC class II glycoproteins. This association is required for functional presentation to antigen-specific T lymphocytes. The proteolytic degradation takes place in antigen-presenting cells, in an acidic, endosomal compartment where antigens arrive after capture and internalization. It is catalyzed by a small number of enzymes, mainly aspartic and thiol proteases, with the cathepsins D and B--in that order--as dominant representatives. Resulting immunogenic protein fragments possess a binding site for mature MHC molecules and a recognition site for T cell receptors; topologically, these sites are interspersed, generally extending over 7-8 consecutive amino acid residues. Binding of peptides by MHC proteins of a particular genotype appears to depend mainly on specific interactions involving a common sequential motif in their primary structure in terms of non-polar and polar/charged amino acid residues and not on a general propensity to adopt a certain regular secondary structure, such as an alpha-helix.
van der Drift
A C
AC
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
van Noort
J M
JM
Krüse
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000737:chemistry / Q000378:metabolism*; D002403:Cathepsins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D011506:Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D006649:Histocompatibility Antigens; D011506:Proteins; D002403:Cathepsins; D010450:Endopeptidases