Linked Life Data

19786555

Source:http://linkedlifedata.com/resource/pubmed/id/19786555

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-10-5
pubmed:abstractText
Immunotherapy of cancer is often performed with altered "analog" peptide Ags optimized for HLA class I binding, resulting in enhanced immunogenicity, but the induced T cell responses require further evaluation. Recently, we demonstrated fine specificity differences and enhanced recognition of naturally presented Ag by T cells after vaccination with natural Melan-A/MART-1 peptide, as compared with analog peptide. In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A(26-35)-specific CD8 T cells derived from both cohorts of patients. Although a strong preference for TRAV12-2 segment usage was present in nearly all patients, usage of particular TRAJ gene segments and CDR3alpha composition differed slightly after vaccination with natural vs analog peptide. Moreover, TCR beta-chain repertoires were broader after natural than analog peptide vaccination. In all patients, we observed a marked conservation of the CDR3beta amino acid composition with recurrent sequences centered on a glycyl-leucyl/valyl/alanyl-glycyl motif. In contrast to viral-specific TCR repertoires, such "public" motifs were primarily expressed by nondominant T cell clonotypes, which contrasted with "private" CDR3beta signatures frequently found in T cell clonotypes that dominated repertoires of individual patients. Interestingly, no differences in functional avidity were observed between public and private T cell clonotypes. Collectively, our data indicate that T cell repertoires generated against natural or analog Melan-A peptide exhibited slightly distinct but otherwise overlapping and structurally conserved TCR features, suggesting that the differences in binding affinity/avidity of TCRs toward pMHC observed in the two cohorts of patients are caused by subtle structural TCR variations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5397-406
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19786555-Amino Acid Sequence, pubmed-meshheading:19786555-Antigens, Neoplasm, pubmed-meshheading:19786555-Autoantigens, pubmed-meshheading:19786555-Base Sequence, pubmed-meshheading:19786555-CD8-Positive T-Lymphocytes, pubmed-meshheading:19786555-Cancer Vaccines, pubmed-meshheading:19786555-HLA-A Antigens, pubmed-meshheading:19786555-HLA-A2 Antigen, pubmed-meshheading:19786555-Humans, pubmed-meshheading:19786555-Immunotherapy, pubmed-meshheading:19786555-MART-1 Antigen, pubmed-meshheading:19786555-Melanoma, pubmed-meshheading:19786555-Molecular Sequence Data, pubmed-meshheading:19786555-Neoplasm Proteins, pubmed-meshheading:19786555-Prospective Studies, pubmed-meshheading:19786555-Protein Conformation, pubmed-meshheading:19786555-Receptors, Antigen, T-Cell, alpha-beta, pubmed-meshheading:19786555-Sequence Alignment, pubmed-meshheading:19786555-Skin Neoplasms
pubmed:year
2009
pubmed:articleTitle
Fine structural variations of alphabetaTCRs selected by vaccination with natural versus altered self-antigen in melanoma patients.
pubmed:affiliation
Division of Experimental Oncology, Multidisciplinary Oncology Center, Lausanne University Hospital, Lausanne, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Clinical Trial, Phase I