Linked Life Data

10605027

Source:http://linkedlifedata.com/resource/pubmed/id/10605027

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-1-19
pubmed:abstractText
The influence of various factors along the processing-loading pathway in limiting the diversity of HLA-B27-bound peptides around a core protein sequence was analyzed. The C5 proteasome subunit-derived RRFFPYYV and RRFFPYYVY peptides are natural B*2705 ligands. The octamer is an allospecific CTL epitope. Digestion of a 27-mer fragment of C5 revealed that both ligands are generated from this precursor substrate with the 20S proteasome in vitro in a ratio comparable to that in the B*2705-bound peptide pool. The C5 sequence allowed to derive a nested set of six additional peptides with 8-11 residues containing the core octamer sequence and the Arg2 motif of HLA-B27, none of which was found in the B27-bound pool. Together, low proteasomal yield, disfavored TAP-binding motifs, and low affinity for B*2705 accounted for the absence of four of the six peptides. The two remaining differed from the natural octamer or nonamer ligands only by an additional N-terminal Ser residue. Their stability in complex with B*2705 was lower than the respective natural ligands, raising the possibility that N-terminal trimming might have favored a shift toward the more stable peptides. The results suggest that the B*2705-bound peptide repertoire has a highly restricted diversity around a core alloantigenic sequence. This is not explained by a single bottleneck feature, but by multiple factors, including proteasomal generation, TAP-binding motifs, MHC-binding efficiency, and perhaps optimized stability through N-terminal trimming. Tapasin-dependent restrictions, although not excluded, were not required to explain the absence in vivo of the particular peptide set in this study.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-37
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10605027-Amino Acid Sequence, pubmed-meshheading:10605027-Antigen Presentation, pubmed-meshheading:10605027-Cell Line, pubmed-meshheading:10605027-Clone Cells, pubmed-meshheading:10605027-Cysteine Endopeptidases, pubmed-meshheading:10605027-Epitopes, T-Lymphocyte, pubmed-meshheading:10605027-HLA-B27 Antigen, pubmed-meshheading:10605027-Humans, pubmed-meshheading:10605027-Isoantigens, pubmed-meshheading:10605027-Ligands, pubmed-meshheading:10605027-Macromolecular Substances, pubmed-meshheading:10605027-Molecular Sequence Data, pubmed-meshheading:10605027-Multienzyme Complexes, pubmed-meshheading:10605027-Oligopeptides, pubmed-meshheading:10605027-Proteasome Endopeptidase Complex, pubmed-meshheading:10605027-Protein Binding, pubmed-meshheading:10605027-T-Lymphocytes, Cytotoxic, pubmed-meshheading:10605027-Transfection
pubmed:year
2000
pubmed:articleTitle
Limited diversity of peptides related to an alloreactive T cell epitope in the HLA-B27-bound peptide repertoire results from restrictions at multiple steps along the processing-loading pathway.
pubmed:affiliation
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Facultad de Ciencias, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't