Chitarra V, Alzari P M, Bentley G A, Bhat T N, Eiselé J L, Houdusse A, Lescar J, Souchon H, Poljak R J
Unité d'Immunologie Structurale (Centre National de la Recherche Scientifique, Unité de Recherches Associée URA 359), Institut Pasteur, Paris, France.
Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7711-5. doi: 10.1073/pnas.90.16.7711.
Although antibodies are highly specific, cross-reactions are frequently observed. To understand the molecular basis of this phenomenon, we studied the anti-hen egg lysozyme (HEL) monoclonal antibody (mAb) D11.15, which cross-reacts with several avian lysozymes, in some cases with a higher affinity (heteroclitic binding) than for HEL. We have determined the crystal structure of the Fv fragment of D11.15 complexed with pheasant egg lysozyme (PHL). In addition, we have determined the structure of PHL, Guinea fowl egg lysozyme, and Japanese quail egg lysozyme. Differences in the affinity of D11.15 for the lysozymes appear to result from sequence substitutions in these antigens at the interface with the antibody. More generally, cross-reactivity is seen to require a stereochemically permissive environment for the variant antigen residues at the antibody-antigen interface.
尽管抗体具有高度特异性，但交叉反应却屡见不鲜。为了解这一现象的分子基础，我们研究了抗鸡卵溶菌酶（HEL）单克隆抗体（mAb）D11.15，它能与多种禽类溶菌酶发生交叉反应，在某些情况下，其亲和力（异嗜性结合）高于与HEL的亲和力。我们已经确定了与雉鸡蛋溶菌酶（PHL）复合的D11.15的Fv片段的晶体结构。此外，我们还确定了PHL、珍珠鸡蛋溶菌酶和日本鹌鹑蛋溶菌酶的结构。D11.15对这些溶菌酶亲和力的差异似乎是由这些抗原在与抗体界面处的序列替换导致的。更普遍地说，交叉反应需要在抗体 - 抗原界面为变异抗原残基提供一个立体化学允许的环境。
