Holán V, Lipoldová M, Demant P
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Immunogenetics. 1996;44(1):27-35. doi: 10.1007/BF02602654.
The inbred strain STS/A exhibits a higher proliferative response in the mixed lymphocyte culture (MLC) to stimulator cells of all 11 tested inbred mouse strains with 10 different major histocompatibility complex (MHC) haplotypes, as well as to stimulation with IL-2 than does the strain BALB/cHeA. However, alloantigen-stimulated BALB/c cells produce more IL-2 than STS/A cells. To study the genetic basis of these differences, we used 20 recombinant congenic strains (RCS) of the CcS/Dem series. Each of these CcS/Dem RC strains contains a different subset of about 12.5% of genes from the STS/A strain and the remaining approximately 87.5% of BALB/c origin genes. As a result the multiple non-linked genes responsible for phenotypic differences between BALB/c and STS/A became separated into different CcS/Dem strains. The strain distribution pattern (SD) of high or low MLC response of individual CcS/Dem strains to stimulator cells of four different strains was almost identical, indicating that differences in responsiveness, rather than the alloantigenic difference itself, determine the magnitude of the response, and that the responsiveness to different alloantigens is largely controlled by the same genes. The SDP of IL-2 stimulation was different from that of MLC responsiveness. The differences in the proliferative responses observed among individual CcS/Dem strains were not due to differences in numbers of CD3+, CD4+ or CD8+ cells or to the observed differences in IL-2 production, and hence they likely reflect genetically determined intrinsic properties of T cells. These results show that a set of non-linked genes controls proliferative responses in MLC irrespective of the MHC haplotype of the stimulator cells, and that stimulation with IL-2 and production of IL-2 are controlled by different subsets of genes. Since the genomes of all RCS are extensively characterized by microsatellite markers, they can be used to map the genes controlling proliferative responsiveness to stimulation with alloantigens and IL-2.
近交系STS/A在混合淋巴细胞培养（MLC）中，对11种经过测试的具有10种不同主要组织相容性复合体（MHC）单倍型的近交小鼠品系的刺激细胞，以及对IL-2刺激的增殖反应，均高于BALB/cHeA品系。然而，同种异体抗原刺激的BALB/c细胞比STS/A细胞产生更多的IL-2。为了研究这些差异的遗传基础，我们使用了CcS/Dem系列的20个重组近交系（RCS）。这些CcS/Dem RC品系中的每一个都包含来自STS/A品系约12.5%的不同基因子集，其余约87.5%的基因来自BALB/c品系。结果，负责BALB/c和STS/A之间表型差异的多个非连锁基因被分离到不同的CcS/Dem品系中。各个CcS/Dem品系对四种不同品系刺激细胞的高或低MLC反应的品系分布模式（SD）几乎相同，这表明反应性的差异而非同种异体抗原差异本身决定了反应的强度，并且对不同同种异体抗原的反应性在很大程度上由相同的基因控制。IL-2刺激的SDP与MLC反应性的SDP不同。在各个CcS/Dem品系中观察到的增殖反应差异并非由于CD3+、CD4+或CD8+细胞数量的差异，也不是由于观察到的IL-2产生差异，因此它们可能反映了T细胞的遗传决定的内在特性。这些结果表明，一组非连锁基因控制MLC中的增殖反应，而与刺激细胞的MHC单倍型无关，并且IL-2刺激和IL-2产生由不同的基因子集控制。由于所有RCS的基因组都通过微卫星标记进行了广泛表征，它们可用于定位控制对同种异体抗原和IL-2刺激的增殖反应性的基因。
