Distinct CDR3 Conformations in TCRs Determine the Level of Cross-Reactivity for Diverse Antigens, but Not the Docking Orientation

作者：Jones Lindsay L; Colf Leremy A; Stone Jennifer D; Garcia K Christopher; Kranz David M^*

来源：The Journal of Immunology, 2008, 181(9): 6255-6264.

DOI：10.4049/jimmunol.181.9.6255

T cells are known to cross-react with diverse peptide MHC Ags through their alpha beta 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 CDR3 alpha 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 CDR3 beta conformations and docking orientations were remarkably similar. Although the CDR3 alpha 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, CDR3a dictated the affinity and level of cross-reactivity, yet it did so without affecting the conserved docking orientation. The Journal of Immunology, 2008, 181: 6255-6264.

• 出版日期2008-11-1