Cook J R, Solheim J C, Connolly J M, Hansen T H
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1995 Jan 1;154(1):47-57.
We have examined the ability of beta 2-m- mice to produce CD4-8+ T cells by generating CD8+ CTLs to a defined ligand. We report here the first demonstration of peptide-specific, self-class I MHC-restricted CTLs from beta 2-m-deficient mice. We have used the KOD mouse, an H-2d beta 2-m- strain, to generate CTLs that recognize the class I MHC molecule Ld in association with one of two Ld-binding immunogenic peptides. Testing of these CTLs on a panel of Ld-binding peptides reveals a high degree of peptide specificity. Peptide-specific CTL bulk cultures from KOD mice differ from those generated in beta 2-m+ mice in that they possess altered affinities for their peptide ligands. In addition, we show that CTLs generated from beta 2-m- mice in the presence of beta 2-m+ stimulator cells and exogenous peptide are specific either for the exogenous peptide or for endogenous peptides that are present in association with Ld on the surface of beta 2-m+ cells, but are not present at detectable levels on beta 2-m- cells. These results demonstrate that positive selection of CD8+ CTLs can occur in vivo on the very low levels of class I MHC found in the KOD mouse. Furthermore, CTLs from the KOD mouse maintain a high degree of peptide specificity despite reduced levels of class I MHC.
我们通过产生针对特定配体的CD8⁺细胞毒性T淋巴细胞（CTL），研究了β2-微球蛋白（β2-m）缺陷小鼠产生CD4⁻8⁺T细胞的能力。我们在此报告首次证明了来自β2-m缺陷小鼠的肽特异性、自身I类主要组织相容性复合体（MHC）限制的CTL。我们使用了KOD小鼠（一种H-2dβ2-m缺陷品系）来产生识别I类MHC分子Ld与两种Ld结合免疫原性肽之一结合的CTL。在一组Ld结合肽上对这些CTL进行测试，发现其具有高度的肽特异性。来自KOD小鼠的肽特异性CTL大量培养物与在β2-m⁺小鼠中产生的CTL不同，因为它们对其肽配体的亲和力发生了改变。此外，我们表明，在β2-m⁺刺激细胞和外源性肽存在的情况下，从β2-m缺陷小鼠产生的CTL对外源性肽或与β2-m⁺细胞表面Ld结合存在的内源性肽具有特异性，但在β2-m缺陷细胞上以可检测水平不存在。这些结果表明，CD8⁺CTL的阳性选择可以在KOD小鼠中发现的极低水平的I类MHC上在体内发生。此外，尽管I类MHC水平降低，但来自KOD小鼠的CTL仍保持高度的肽特异性。
