Landry R C, Klimowicz A C, Lavictoire S J, Borisova S, Kottachchi D T, Lorimer I A, Evans S V
Department of Biochemistry Microbiology and Immunology, University of Ottawa, 451 Smyth, Ottawa, K1H 8M5, Canada.
J Mol Biol. 2001 May 18;308(5):883-93. doi: 10.1006/jmbi.2001.4628.
Epitope mapping studies and the determination of the structure to 1.8 A resolution have been carried out for the antigen-binding fragment MR1 in complex with peptide antigen. MR1 is specific for the novel fusion junction of the mutant epidermal growth factor receptor EGFRvIII and has been reported to have a high degree of specificity for the mutant EGFRvIII over the wild-type EGF receptor. The structure of the complex shows that the peptide antigen residue side-chains found by epitope mapping studies to be critical for recognition are accommodated in pockets on the surface of the Fv. However, the most distinctive portion of the peptide antigen, the novel fusion glycine residue, makes no contact to the Fv and does not contribute directly to the epitope. The specificity of MR1 lies in the ability of this glycine residue to assume the restricted conformation needed to form a type II' beta-hairpin turn more easily, and demonstrates that a peptide antigen can be used to generate a conformational epitope.
已对与肽抗原结合的抗原结合片段MR1进行了表位作图研究，并将其结构解析至1.8埃分辨率。MR1对突变型表皮生长因子受体EGFRvIII的新型融合连接具有特异性，并且据报道，与野生型表皮生长因子受体相比，它对突变型EGFRvIII具有高度特异性。复合物的结构表明，表位作图研究发现对识别至关重要的肽抗原残基侧链容纳在Fv表面的口袋中。然而，肽抗原最独特的部分，即新型融合甘氨酸残基，不与Fv接触，也不直接构成表位。MR1的特异性在于该甘氨酸残基能够更轻松地形成II'型β-发夹转角所需的受限构象，并证明肽抗原可用于产生构象表位。
