Hennecke J, Carfi A, Wiley D C
Department of Molecular and Cellular Biology, Harvard University, Howard Hughes Medical Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA.
EMBO J. 2000 Nov 1;19(21):5611-24. doi: 10.1093/emboj/19.21.5611.
An alphabeta T-cell receptor (alphabetaTCR)/hemagglutinin (HA) peptide/human leukocyte antigen (HLA)-DR1 complex was stabilized by flexibly linking the HA peptide with the human HA1.7 alphabetaTCR, to increase the local concentration of the interacting proteins once the peptide has been loaded onto the major histocompatibility complex (MHC) molecule. The structure of the complex, determined by X-ray crystallography, has a binding mode similar to that of the human B7 alphabetaTCR on a pMHCI molecule. Twelve of the 15 MHC residues contacted are at the same positions observed earlier in class I MHC/peptide/TCR complexes. One contact, to an MHC loop outside the peptide-binding site, is conserved and specific to pMHCII complexes. TCR gene usage in the response to HA/HLA-DR appears to conserve charged interactions between three lysines of the peptide and acidic residues on the TCR.
通过将血凝素（HA）肽与人HA1.7αβT细胞受体（αβTCR）灵活连接，稳定了αβT细胞受体（αβTCR）/血凝素（HA）肽/人白细胞抗原（HLA）-DR1复合物，一旦肽加载到主要组织相容性复合体（MHC）分子上，就可提高相互作用蛋白的局部浓度。通过X射线晶体学确定的该复合物结构，其结合模式类似于pMHCI分子上的人B7αβTCR。所接触的15个MHC残基中有12个处于I类MHC/肽/TCR复合物中早期观察到的相同位置。与肽结合位点外的MHC环的一个接触是保守的，且是pMHCII复合物特有的。对HA/HLA-DR反应中的TCR基因使用似乎保留了肽的三个赖氨酸与TCR上酸性残基之间的带电相互作用。
