Germ Line-governed Recognition of a Cancer Epitope by an Immunodominant Human T-cell Receptor

Cole, David K., Yuan, Fang, Rizkallah, PierreJ, Miles, John J., Gostick, Emma, Price, David A., Gao, George F., Jakobsen, Bent K. and Sewell, Andrew K. (2009) Germ Line-governed Recognition of a Cancer Epitope by an Immunodominant Human T-cell Receptor. Journal of Biological Chemistry, 284 40: 27281-27289. doi:10.1074/jbc.M109.022509

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Author Cole, David K.
Yuan, Fang
Rizkallah, PierreJ
Miles, John J.
Gostick, Emma
Price, David A.
Gao, George F.
Jakobsen, Bent K.
Sewell, Andrew K.
Title Germ Line-governed Recognition of a Cancer Epitope by an Immunodominant Human T-cell Receptor
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2009-10
Sub-type Article (original research)
DOI 10.1074/jbc.M109.022509
Open Access Status File (Publisher version)
Volume 284
Issue 40
Start page 27281
End page 27289
Total pages 9
Place of publication United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
CD8+ T-cells specific for MART-1-(26-35), a dominant melanoma epitope restricted by human leukocyte antigen (HLA)-A*0201, are exceptionally common in the naive T-cell repertoire. Remarkably, the TRAV12-2 gene is used to encode the T-cell receptor α (TCRα) chain in >87% of these T-cells. Here, the molecular basis for this genetic bias is revealed from the structural and thermodynamic properties of an archetypal TRAV12-2-encoded TCR complexed to the clinically relevant heteroclitic peptide, ELAGIGILTV, bound to HLA-A*0201 (A2-ELA). Unusually, the TRAV12-2 germ line-encoded regions of the TCR dominate the major atomic contacts with the peptide at the TCR/A2-ELA interface. This "innate" pattern of antigen recognition probably explains the unique characteristics and extraordinary frequencies of CD8+ T-cell responses to this epitope. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Keyword Complex Class-i
Melanoma Patients
Peptide vaccines
Structural Basis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 68 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 12 Nov 2009, 12:02:29 EST by Mr Andrew Martlew