Rojo S, López D, Calvo V, López de Castro J A
Department of Immunology, Fundación Jiménez Díaz, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
J Immunol. 1991 Jan 15;146(2):634-42.
Alloreactive CTL responses generate a great variety of clonal specificities. Such diversity may be related to recognition of multiple peptides constitutively bound to any given MHC alloantigen. Among human alloreactive CTL, only a fraction of the clones lyse mouse P815 cells expressing class I HLA proteins. In this study the fine specificity of HLA-B27 allorecognition on human or mouse cells by five human HLA-B27-specific CTL clones was comparatively analyzed. This was done to examine what degree of variation in epitope structure is compatible with recognition of HLA Ag on mouse cells. Nine site-specific HLA-B27 mutants were expressed on both human and mouse cells, after DNA-mediated gene transfer, to construct two analogous series of target cells. The reaction patterns of four of the five CTL clones with these cell panels were compatible with conservation of their corresponding epitopes upon expression of HLA-B27 on mouse cells. The reaction pattern of the fifth clone was different with either cell panel, indicating that its epitope was structurally altered on mouse cells. It also suggested a selectively increased expression of the determinant on these cells. The results suggest that most of the epitopes recognized by allospecific CTL clones reacting across species are either independent of any bound peptide or involve identical peptides from both cell types. However, some of these clones recognize alloantigen-bound peptides that are somewhat different in structure depending on the cell type, and may be expressed at the mouse cell surface in greater amounts. Such peptides could arise from related proteins in both species, and be polymorphic as a result of phylogenetic divergence.
同种异体反应性CTL反应产生多种克隆特异性。这种多样性可能与对组成性结合到任何给定MHC同种异体抗原上的多种肽的识别有关。在人类同种异体反应性CTL中，只有一小部分克隆能够裂解表达I类HLA蛋白的小鼠P815细胞。在本研究中，对五个人类HLA - B27特异性CTL克隆对人或小鼠细胞上HLA - B27的同种异体识别精细特异性进行了比较分析。这样做是为了检查表位结构的何种程度的变异与小鼠细胞上HLA抗原的识别相容。在DNA介导的基因转移后，在人和小鼠细胞上表达了九个位点特异性HLA - B27突变体，以构建两个类似的靶细胞系列。五个CTL克隆中的四个与这些细胞组的反应模式与在小鼠细胞上表达HLA - B27时其相应表位的保守性相容。第五个克隆与任何一个细胞组的反应模式都不同，表明其表位在小鼠细胞上结构发生了改变。这也表明该决定簇在这些细胞上的表达选择性增加。结果表明，跨物种反应的同种特异性CTL克隆识别的大多数表位要么独立于任何结合肽，要么涉及两种细胞类型中相同的肽。然而，其中一些克隆识别的同种抗原结合肽根据细胞类型在结构上略有不同，并且可能在小鼠细胞表面大量表达。此类肽可能源自两种物种中的相关蛋白，并由于系统发育分歧而具有多态性。
