The 39- to 43-amino acid amyloid beta protein (beta AP), which is deposited as amyloid in Alzheimer's disease, is encoded as an internal peptide that begins 99 residues from the carboxyl terminus of a 695- to 770-amino acid glycoprotein referred to as the amyloid beta protein precursor (beta APP). To clarify the processing that produces amyloid, carboxyl-terminal derivatives of the beta APP were analyzed. This analysis showed that the beta APP is normally processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives. The two largest derivatives in human brain have the entire beta AP at or near their amino terminus and are likely to be intermediates in the pathway leading to amyloid deposition.
Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen in MS, but the disease-associated epitopes have not been determined. Using overlapping and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects (HS). Short-term T cell lines (TCL) were selected against each peptide using microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95-116-specific TCL were most efficiently generated and the frequency was significantly higher in MS compared with HS (P < 0.05). When compared between DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were also increased in DR2,w15+ MS (P < 0.025). Using DR gene-transfected L cells, we could show that the DRB1*1501 product of the DR2 haplotype presents PLP 95-116 to TCL selected against the peptide. These results imply that PLP 95-116 represents a major epitope for the DR2,w15+ MS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.