Reiser Jean-Baptiste, Darnault Claudine, Grégoire Claude, Mosser Thomas, Mazza Gilbert, Kearney Alice, van der Merwe P Anton, Fontecilla-Camps Juan Carlos, Housset Dominique, Malissen Bernard
Laboratoire de Cristallographie et Cristallogenèse des Protéines, Institut de Biologie Structurale J.-P. Ebel, CEA-CNRS-UJF, 41 rue Jules Horowitz, F-38027 Grenoble Cedex 1, France.
Nat Immunol. 2003 Mar;4(3):241-7. doi: 10.1038/ni891. Epub 2003 Feb 3.
T cell receptor (TCR) binding degeneracy lies at the heart of several physiological and pathological phenomena, yet its structural basis is poorly understood. We determined the crystal structure of a complex involving the BM3.3 TCR and an octapeptide (VSV8) bound to the H-2K(b) major histocompatibility complex molecule at a 2.7 A resolution, and compared it with the BM3.3 TCR bound to the H-2K(b) molecule loaded with a peptide that has no primary sequence identity with VSV8. Comparison of these structures showed that the BM3.3 TCR complementarity-determining region (CDR) 3alpha could undergo rearrangements to adapt to structurally different peptide residues. Therefore, CDR3 loop flexibility helps explain TCR binding cross-reactivity.
T细胞受体（TCR）结合简并性是多种生理和病理现象的核心，但对其结构基础却知之甚少。我们确定了一个复合物的晶体结构，该复合物包含BM3.3 TCR和与H-2K(b)主要组织相容性复合体分子结合的八肽（VSV8），分辨率为2.7埃，并将其与结合了与VSV8无一级序列同一性的肽的H-2K(b)分子的BM3.3 TCR进行比较。这些结构的比较表明，BM3.3 TCR互补决定区（CDR）3α可发生重排以适应结构不同的肽残基。因此，CDR3环的灵活性有助于解释TCR结合交叉反应性。
