IMMUNE-RESPONSE GENE-FUNCTION CORRELATES WITH THE EXPRESSION OF AN IA-ANTIGEN .2. A QUANTITATIVE DEFICIENCY IN A-EPSILON-E-ALPHA COMPLEX EXPRESSION CAUSES A CORRESPONDING DEFECT IN ANTIGEN-PRESENTING CELL-FUNCTION
IMMUNE-RESPONSE GENE-FUNCTION CORRELATES WITH THE EXPRESSION OF AN IA-ANTIGEN .2. A QUANTITATIVE DEFICIENCY IN A-EPSILON-E-ALPHA COMPLEX EXPRESSION CAUSES A CORRESPONDING DEFECT IN ANTIGEN-PRESENTING CELL-FUNCTION
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DOI：
10.1084/jem.155.2.508
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发表时间：
1982-01-01
影响因子：
15.3
通讯作者：
SCHWARTZ, RH
中科院分区：
文献类型：
--
作者：
MATIS, LA;JONES, PP;SCHWARTZ, RH
实验进行了探索的作用，补充主要组织相容性复合体（MHC）连接的免疫反应Ir基因在小鼠T细胞增殖反应的球蛋白抗原鸽细胞色素c。I-E-亚区编码的、结构同源的E α.通过低应答B10.A（4 R）（I-Ak）或B10.S（I-As）小鼠与4只低应答E α-E10.A（4 R）（I-Ak）或E10.S（I-As）小鼠之间的F1杂种对鸽子细胞色素c的高应答性的互补，证明了来自不同单倍型的具有血清学特异性Ia.7的链。带有单倍型。该Ir基因功能与来自这些相同F1品系的抗原脉冲脾细胞刺激来自B10.A或B10.S（9 R）小鼠的鸽细胞色素c引发的T细胞的能力以及与2-链Ia抗原复合物Ae：E α的细胞表面表达直接相关，带有由单克隆抗Ia抗体Y-17识别的构象或组合决定簇。表达Ia.7阳性I-E亚区编码的E α.链，未能与B10.A（4 R）或B10.S小鼠在鸽子细胞色素c的反应中互补。（B10.A（4R）×B10.PL）F1和（B10.S ×. B10.PL）F1小鼠确实表达%w%000004%%和.**图形 **。在其细胞表面，尽管相对于.** 的量减少图形 **。在相应的F1菌株中发现复合物。Ia抗原表达的这种定量差异与将鸽子细胞色素c呈递给Bio.A和B10.S（9 R）长期T细胞系的能力差异相关。因此，（B10.A（4 R）×B10.PL）F1脾细胞需要高10倍的抗原剂量来诱导与（B10.A（4 R）× F1脾细胞相同的刺激。B10.D2）F1脾细胞。Y-17，其与Ae：E α反应。几种菌株的分子，在（B10.A（4 R）× B10.A）存在下，对B10.A T细胞对鸽子细胞色素c的增殖反应具有更大的抑制作用。B10.PL）F1脾细胞比在（B10.A（4 R）× B10.PL）F1脾细胞存在下的细胞数高。B10.D2）F1脾细胞。这些功能数据与Ir基因互补的分子模型一致，其中适当的2-链Ia分子在抗原呈递细胞（APC）表面作为限制性元件发挥作用。T细胞增殖反应的幅度是名义抗原浓度和APC上表达的Ia抗原量的函数。Ia抗原的细胞表面表达的定量缺陷与抗原呈递功能的相应相对缺陷的直接相关性提供了强有力的独立证据，即I区编码的Ia抗原是MHC连锁的Ir基因的产物。
Experiments were performed to explore the role of complementing major histocompatibility complex (MHC)-linked immune response Ir genes in the murine T cell proliferative response to the globular protein antigen pigeon cytochrome c. The functional equivalence of I-E-subregion-encoded, structurally homologous E.alpha. chains from different haplotypes bearing the serologic specificity Ia.7 was demonstrated by the complementation for high responsiveness to pigeon cytochrome c of F1 hybrids between low responder B10.A(4R) (I-Ak) or B10.S (I-As) mice and 4 low responder E.alpha.-bearing haplotypes. This Ir gene function correlated directly with the ability of antigen-pulsed spleen cells from these same F1 strains to stimulate pigeon cytochrome c-primed T cells from B10.A or B10.S(9R) mice and with the cell surface expression of the 2-chain Ia antigenic complex, Ae:E.alpha., bearing the conformational or combinatorial determinant recognized by the monoclonal anti-Ia antibody, Y-17. The B10.PL strain (H-2u), which expresses an Ia.7-positive I-E-subregion-encoded E.alpha. chain, failed to complement with B10.A(4R) or B10.S mice in the response to pigeon cytochrome c. (B10.A(4R) .times. B10.PL)F1 and (B10.S .times. B10.PL)F1 mice do express %w%000004%% and .**GRAPHIC**. on their cell surface, although in reduced amounts relative to .**GRAPHIC**. complexes found in corresponding F1 strains. This quantitative difference in Ia antigen expression correlated with a difference in the ability to present pigeon cytochrome c to Bio.A and B10.S(9R) long-term T cell lines. Thus, (B10.A(4R) .times. B10.PL)F1 spleen cells required a 10-fold higher antigen dose to induce the same stimulation as (B10.A(4R) .times. B10.D2)F1 spleen cells. Y-17, which reacts with Ae:E.alpha. molecules of several strains, had a greater inhibitory effect on the proliferative response to pigeon cytochrome c of B10.A T cells in the presence of (B10.A(4R) .times. B10.PL)F1 spleen cells than in the presence of (B10.A(4R) .times. B10.D2)F1 spleen cells. These functional data are consistent with the molecular model for Ir gene complementation in which appropriate 2-chain Ia molecules function at the antigen-presenting cell (APC) surface as restriction elements. The magnitude of the T cell proliferative response is a function of both the concentration of nominal antigen and of the amount of Ia antigen expressed on the APC. The direct correlation of a quantitative deficiency in cell surface expression of an Ia antigen with a corresponding relative defect in antigen-presenting function provides strong independent evidence that the I-region-encoded Ia antigens are the products of the MHC-linked Ir genes.