Dutz J P, Tsomides T J, Kageyama S, Rasmussen M H, Eisen H N
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Mol Immunol. 1994 Sep;31(13):967-75. doi: 10.1016/0161-5890(94)90091-4.
The alloreactive CD8+ cytotoxic T lymphocyte (CTL) clone 2C was previously shown to recognize complexes made up of the class I MHC (MHC-I) molecule Ld and an octapeptide (LSPFPFDL, termed p2Ca) isolated from tissues of H-2d mice. Because peptide p2Ca has also been found in BALB.B (H-2b) mice, the strain from which clone 2C originated, the question arises as to whether these T cells can recognize peptide p2Ca in association with a self MHC protein of the H-2b haplotype. Here we show that 2C CTL do indeed recognize peptide p2Ca in association with Kb on the surface of H-2b cells or on transfected cells expressing Kb, but that an approximately 1000-fold higher concentration of this peptide is required to sensitize Kb+ than Ld+ target cells for lysis by 2C cells. However, the peptide's binding to Kb was not much weaker than to Ld, with only an approximately 10-fold difference in the respective equilibrium constants. These results predict that the T cell receptor (TcR) of clone 2C has a much lower intrinsic affinity for p2Ca-Kb complexes than for p2Ca-Ld complexes, and they provide some quantitative limits on the requirements for triggering T cell-mediated autoimmune reactivity.
同种异体反应性CD8 + 细胞毒性T淋巴细胞（CTL）克隆2C先前已被证明可识别由I类主要组织相容性复合体（MHC-I）分子Ld和从H-2d小鼠组织中分离出的八肽（LSPFPFDL，称为p2Ca）组成的复合物。由于在克隆2C起源的BALB.B（H-2b）小鼠中也发现了肽p2Ca，因此就产生了一个问题，即这些T细胞是否能识别与H-2b单倍型的自身MHC蛋白结合的肽p2Ca。在这里，我们表明2C CTL确实能识别与H-2b细胞表面或表达Kb的转染细胞上的Kb结合的肽p2Ca，但使Kb + 靶细胞对2C细胞裂解敏感所需的该肽浓度比Ld + 靶细胞高约1000倍。然而，该肽与Kb的结合并不比与Ld的结合弱很多，各自的平衡常数仅相差约10倍。这些结果预测，克隆2C的T细胞受体（TcR）对p2Ca-Kb复合物的内在亲和力比对p2Ca-Ld复合物的内在亲和力低得多，并且它们为触发T细胞介导的自身免疫反应性的要求提供了一些定量限制。
