McElligott D L, Sorger S B, Matis L A, Hedrick S M
Department of Biology, University of California, San Diego, La Jolla 92093.
J Immunol. 1988 Jun 15;140(12):4123-31.
Previous experiments have demonstrated that the immune response of MHC congenic mice to pigeon cytochrome c is under Ir gene control. Expression of I-E-encoded gene products influences both the magnitude and fine specificity of the Th cell response to pigeon cytochrome c and phylogenetic derivatives. Results of those experiments implicate both determinant selection and repertoire selection as mechanisms of Ir gene control in this system. In this report we have compared the TCR expressed in pigeon cytochrome c-reactive Th cells from B10.A(I-Ek), B10.A(5R) (I-Eb), and B10.S(9R) (I-Es) mice. The B10.A(5R) strain is a low responder to pigeon cytochrome c, but in response to moth cytochrome c this strain produces T cells which respond to pigeon or moth cytochrome c on B10.A APC. These cells are phenotypically identical to the predominant clonal phenotype seen in the B10.A response to pigeon cytochrome c. In this report, we show that the B10.A and B10.A(5R) pigeon cytochrome c-reactive T cells express essentially identical T cell receptors. These results, coupled with recent studies reporting a relatively low affinity for I-Eb molecules by pigeon cytochrome c peptides compared with moth cytochrome c peptides, strongly argue that the immune response defect in the B10.A(5R) strain is due to a defect in Ag presentation (determinant selection). In contrast, B10.A and B10.S(9R) strains are high responders to pigeon cytochrome c. Both strains produce T cell clones which are capable of responding to cytochrome c presented by either B10.A or B10.S(9R) APC in vitro. We show that, even in T cells with this MHC restriction degeneracy, the TCR expressed in the two strains are different. Because the APC of both strains can clearly present the cytochrome c Ag, we conclude that the differential expression of the TCR in the responses is due to a T cell repertoire selection difference in the two strains. Thus, for the response to one Ag in three MHC congenic strains, there exists evidence that both determinant selection and repertoire selection can be mechanisms of Ir gene control of an immune response.
先前的实验表明，MHC同基因小鼠对鸽细胞色素c的免疫反应受Ir基因控制。I-E编码基因产物的表达影响Th细胞对鸽细胞色素c及其系统发育衍生物反应的强度和精细特异性。这些实验结果表明，决定簇选择和库选择都是该系统中Ir基因控制的机制。在本报告中，我们比较了来自B10.A(I-Ek)、B10.A(5R)(I-Eb)和B10.S(9R)(I-Es)小鼠的鸽细胞色素c反应性Th细胞中表达的TCR。B10.A(5R)品系对鸽细胞色素c反应较弱，但对蛾细胞色素c有反应，该品系产生的T细胞可对B10.A抗原呈递细胞上的鸽或蛾细胞色素c作出反应。这些细胞在表型上与B10.A对鸽细胞色素c反应中所见的主要克隆表型相同。在本报告中，我们表明B10.A和B10.A(5R)鸽细胞色素c反应性T细胞表达基本相同的T细胞受体。这些结果，再加上最近的研究报告称，与蛾细胞色素c肽相比，鸽细胞色素c肽对I-Eb分子的亲和力相对较低，有力地证明了B10.A(5R)品系的免疫反应缺陷是由于抗原呈递缺陷（决定簇选择）。相比之下，B10.A和B10.S(9R)品系对鸽细胞色素c反应较强。两个品系均产生能够在体外对B10.A或B10.S(9R)抗原呈递细胞呈递的细胞色素c作出反应的T细胞克隆。我们表明，即使在具有这种MHC限制性简并性的T细胞中，两个品系中表达的TCR也是不同的。由于两个品系的抗原呈递细胞都能清楚地呈递细胞色素c抗原，我们得出结论，反应中TCR的差异表达是由于两个品系中T细胞库选择的差异。因此，对于三种MHC同基因品系对一种抗原的反应，有证据表明决定簇选择和库选择都可能是免疫反应中Ir基因控制的机制。
