Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.56 (insulin-degrading enzyme)
 737 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T cell responses against complex antigens are often directed against a limited set of immunodominant determinants. We have studied this phenomenon at the level of cellularly processed peptides recognized by CTL in the B6 anti-BALB.B minor histocompatibility (H) barrier, comprising at least 29 antigen loci. B6 anti-BALB.B CTL always recognized three reverse phase HPLC fractions in BALB.B eluates, whether the latter were obtained from cell lysates or immunoaffinity purified class I molecules. One of these immunodominant epitopes (termed IDE-1) was H-2Db restricted, and two (termed IDE-2 and IDE-3) were H-2Kb restricted. B6 mice were immunized with spleen cells from B6 congenic mice carrying single minor H loci from BALB.B with the aim to assign IDE to given minor H loci and to investigate whether additional epitopes could be identified in the absence of the immunodominant ones. IDE-3 was found to be associated to the locus H-28; in addition five so called cryptic epitopes were defined. Induction of CTL against these epitopes required immunization with cells of the congenic strain; BALB.B spleen cells failed to immunize. One subgroup of these epitopes (those associated to H-8, H-19 and H-25) were nevertheless found to be processed and loaded in class I molecules of BALB.B cells, while there was no evidence for this for H-35 and H-36. For 10 additional congenic strains, no CTL response was detected. The results are discussed in relation to the genetic and molecular basis of minor H antigens, and mechanisms for epitope dominance operating at the level of the APC or responding T cells.
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PMID:Dominant and cryptic antigens in the MHC class I restricted T cell response across a complex minor histocompatibility barrier: analysis and mapping by elution of cellular peptides. 757

The term "cryptome" refers to the subset of cryptic peptides with bioactivities that are often unpredictable and very different from the parent protein. These cryptic peptides are generated by proteolytic cleavage of proteases, whose identification in vivo can be very challenging. In this work, we show that insulin-degrading enzyme (IDE) is able to degrade specific amino acid sequences present in the neuropeptide pro-NPFFA (NPFF precursor), generating some cryptic peptides that are also observed after incubation with rat brain cortex homogenate. The reported experimental findings support the increasingly accredited hypothesis, according to which, due to its wide substrate selectivity, IDE is involved in a wide variety of physiopathological processes.
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PMID:Metabolism of cryptic peptides derived from neuropeptide FF precursors: the involvement of insulin-degrading enzyme. 2524 77