Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation

Lindsay L. Jones, Leremy A. Colf, Jennifer D. Stone, K. Christopher Garcia, David M. Kranz

Research output: Contribution to journalArticle

Abstract

T cells are known to cross-react with diverse peptide MHC Ags through their αβ TCR. To explore the basis of such cross-reactivity, we examined the 2C TCR that recognizes two structurally distinct ligands, SIY-K b and alloantigen QL9-L d . In this study we characterized the cross-reactivity of several high-affinity 2C TCR variants that contained mutations only in the CDR3α loop. Two of the TCR lost their ability to cross-react with the reciprocal ligand (SIY-K b ), whereas another TCR (m67) maintained reactivity with both ligands. Crystal structures of four of the TCRs in complex with QL9-L d showed that CDR1, CDR2, and CDR3β conformations and docking orientations were remarkably similar. Although the CDR3α loop of TCR m67 conferred a 2000-fold higher affinity for SIY-K b , the TCR maintained the same docking angle on QL9-L d as the 2C TCR. Thus, CDR3α dictated the affinity and level of cross-reactivity, yet it did so without affecting the conserved docking orientation.

Original languageEnglish (US)
Pages (from-to)6255-6264
Number of pages10
JournalJournal of Immunology
Volume181
Issue number9
DOIs
StatePublished - Nov 1 2008

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Ligands
Antigens
Isoantigens
T-Lymphocytes
Peptides
Mutation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation. / Jones, Lindsay L.; Colf, Leremy A.; Stone, Jennifer D.; Garcia, K. Christopher; Kranz, David M.

In: Journal of Immunology, Vol. 181, No. 9, 01.11.2008, p. 6255-6264.

Research output: Contribution to journalArticle

Jones, Lindsay L. ; Colf, Leremy A. ; Stone, Jennifer D. ; Garcia, K. Christopher ; Kranz, David M. / Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation. In: Journal of Immunology. 2008 ; Vol. 181, No. 9. pp. 6255-6264.
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