Brown J H, Jardetzky T, Saper M A, Samraoui B, Bjorkman P J, Wiley D C
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Nature. 1988 Apr 28;332(6167):845-50. doi: 10.1038/332845a0.
Class II and class I histocompatibility molecules allow T cells to recognize 'processed' polypeptide antigens. The two polypeptide chains of class II molecules, alpha and beta, are each composed of two domains (for review see ref. 6); the N-terminal domains of each, alpha 1 and beta 1, are highly polymorphic and appear responsible for binding peptides at what appears to be a single site and for being recognized by MHC-restricted antigen-specific T cells. Recently, the three-dimensional structure of the foreign antigen binding site of a class I histocompatibility antigen has been described. Because a crystal structure of a class II molecule is not available, we have sought evidence in class II molecules for the structural features observed in the class I binding site by comparing the patterns of conserved and polymorphic residues of twenty-six class I and fifty-four class II amino acid sequences. The hypothetical class II foreign-antigen binding site we present is consistent with mutation experiments and provides a structural framework for proposing peptide binding models to help understand recent peptide binding data.
II类和I类组织相容性分子使T细胞能够识别“加工后的”多肽抗原。II类分子的两条多肽链，α链和β链，每条都由两个结构域组成（综述见参考文献6）；每条链的N端结构域，α1和β1，具有高度多态性，似乎负责在一个位点结合肽，并被MHC限制性抗原特异性T细胞识别。最近，已描述了I类组织相容性抗原的外来抗原结合位点的三维结构。由于没有II类分子的晶体结构，我们通过比较26个I类和54个II类氨基酸序列的保守和多态性残基模式，在II类分子中寻找I类结合位点中观察到的结构特征的证据。我们提出的假设性II类外来抗原结合位点与突变实验一致，并为提出肽结合模型提供了结构框架，以帮助理解最近的肽结合数据。
