Sykulev Y, Brunmark A, Tsomides T J, Kageyama S, Jackson M, Peterson P A, Eisen H N
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11487-91. doi: 10.1073/pnas.91.24.11487.
We report here that the intrinsic affinities of the antigen-specific T-cell receptors (TCR) of two unrelated CD8+ T-cell clones for their respective peptide-major histocompatibility complex (MHC) ligands are higher than the values generally thought to prevail for TCR. The TCR of one clone (2C) binds an allogeneic class I MHC protein (Ld) in association with an alpha-ketoglutarate dehydrogenase nonapeptide (QLSPFPFDL, termed QL9) with an intrinsic affinity (intrinsic equilibrium association constant) of 1-2 x 10(7) M-1. The TCR of the other clone (4G3) binds a syngeneic class I MHC protein (Kb) in association with an ovalbumin octapeptide (SIINFEKL, termed pOV8) with an intrinsic affinity of 1.5 x 10(6) M-1. A comparison of the two clones, combined with current views of T-cell repertoire selection in the thymus, leads us to propose that TCR affinities are generally likely to be higher for allogeneic MHC-peptide complexes than for syngeneic MHC-peptide complexes.
我们在此报告,两个不相关的CD8+ T细胞克隆的抗原特异性T细胞受体(TCR)对其各自的肽-主要组织相容性复合体(MHC)配体的内在亲和力高于一般认为的TCR普遍存在的值。一个克隆(2C)的TCR与一种同种异体I类MHC蛋白(Ld)结合,该蛋白与α-酮戊二酸脱氢酶九肽(QLSPFPFDL,称为QL9)结合,其内在亲和力(内在平衡缔合常数)为1-2×10⁷ M⁻¹。另一个克隆(4G3)的TCR与一种同基因I类MHC蛋白(Kb)结合,该蛋白与卵清蛋白八肽(SIINFEKL,称为pOV8)结合,其内在亲和力为1.5×10⁶ M⁻¹。对这两个克隆的比较,结合目前关于胸腺中T细胞库选择的观点,使我们提出,同种异体MHC-肽复合物的TCR亲和力通常可能高于同基因MHC-肽复合物。