Sequences that flank subdominant and cryptic epitopes influence the proteolytic generation of MHC class I-presented peptides
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2001-02-07Keywords
Amino Acid SequenceAnimals
Antigen Presentation
Chickens
Cricetinae
Cysteine Endopeptidases
H-2 Antigens
Hybridomas
Hydrolysis
Immunodominant Epitopes
Mice
Molecular Sequence Data
Multienzyme Complexes
Oligopeptides
Ovalbumin
Peptide Fragments
Proteasome Endopeptidase Complex
Tumor Cells, Cultured
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The proteasome has been shown to make the proper C-terminal cleavage for the generation of several immunodominant class I-presented peptides whereas aminopeptidases generate their proper N termini. In this study, we show that these two distinct proteolytic processes are also involved in generating a subdominant OVA peptide KVVRFDKL (K-L). Moreover, proteasome inhibitors did not enhance the presentation of any K-L construct, suggesting that destruction of this peptide by proteasomes, if any, does not limit its presentation. We have further examined in intact cells the influence of residues flanking this epitope on these proteolytic processes. When the N-terminal flanking residues of K-L are fused to an immunodominant OVA peptide SIINFEKL (S-L), the presentation of S-L is reduced as compared with a construct with its natural flanking sequence and was not inhibited (or enhanced) by proteasome inhibitors. Similarly, a reduction in presentation was observed when the C-terminal flanking residues of the subdominant epitope were attached to S-L. A detailed analysis revealed that the Pro at the P1' position of K-L was responsible for this reduction, and presentation of these C-terminally extended constructs was sensitive to proteasome inhibitor. The study suggests that both the N- and C-terminal flanks of the subdominant peptide are suboptimal for Ag presentation. Moreover, three of four C-terminal residues that flank other subdominant or cryptic epitopes in OVA reduced the presentation of S-L. Therefore, the residues that flank the C termini of several subdominant and cryptic epitopes are often suboptimal for cleavage and may contribute to the phenomenon of immunodominance.Source
J Immunol. 2000 Apr 15;164(8):4003-10.
DOI
10.4049/jimmunol.164.8.4003Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38260PubMed ID
10754291Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.164.8.4003