Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in A(e):E(a), complex expression causes a corresponding defect in antigen-presenting cell function
Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in A(e):E(a), complex expression causes a corresponding defect in antigen-presenting cell function
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免疫应答基因功能与 Ia 抗原的表达相关。
DOI：
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发表时间：
1982
影响因子：
15.3
通讯作者：
R. Schwartz
中科院分区：
文献类型：
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作者：
L. Matis;P. Jones;D. Murphy;SM Hedrick;E. Lerner;C. Janeway;J. McNicholas;R. Schwartz
我们进行了一系列的实验来探索主要组织相容性复合体（MHC）相关的免疫反应Ir基因在小鼠T细胞对球蛋白抗原鸽子细胞色素c的增殖反应中的作用。来自不同单倍型的具有血清学特异性Ia.7的同源E(a)链在F(1)杂交体与低应答者b10之间互补，对鸽子细胞色素c具有高应答性。A(4R) （I-A (k)）或b10。S （I-A(8)）小鼠和4个低应答E(a)基因单倍型。此外，这种Ir基因功能与来自这些F(1)菌株的抗原脉冲脾细胞刺激来自B10的鸽子细胞色素c-启动T细胞的能力直接相关。A或B10。S（9R）小鼠，细胞表面表达双链Ia抗原复合物A(e): e (A)，携带单克隆抗Ia抗体Y-17识别的构象或组合决定因子。B10. pl株（H-2(u)）表达一条i7阳性的I-E-亚区编码的E(a)链，但无法与B10互补。A（4R）或B10。然而，(B10。A（4R） × B10. pl)F(1)和（B10. pl）S × B10.PL)F(1)小鼠在其细胞表面确实表达A(k)(e): e (u)(A)和A(8)(e): e (u)(A)，尽管相对于相应的F(1)菌株中发现的A(k， S)(e): e (k,d,p,r)(A)复合物的数量减少。这种Ia抗原表达的数量差异与鸽子细胞色素c到b10表达能力的差异相关。A和B。S（9R）长期T细胞系。因此,(B10。A（4R） × B10. pl)F(1)脾细胞需要比（B10）高10倍的抗原剂量才能诱导相同的刺激。A（4r） × b10。D2)F(1)脾细胞。此外，单克隆抗体Y-17能与多种菌株的A(e): e (A)分子发生反应，对B10对鸽子细胞色素c的增殖反应有较大的抑制作用。A T细胞在（B10）的存在下。A(4R) X B10. pl)F(1)脾脏细胞比（B10）存在时明显减少。A(4r) xb10。D2)F(1)脾细胞。这些功能数据与随附报告中的生化和血清学数据一致，与Ir基因互补的分子模型一致，其中适当的双链Ia分子在抗原呈递细胞（APC）表面作为限制元件起作用。此外，他们清楚地表明，T细胞增殖反应的大小是名义抗原浓度和在APC上表达的Ia抗原量的函数。最后，细胞表面Ia抗原表达的数量缺陷与相应的抗原呈递功能的相对缺陷之间的直接关联提供了强有力的独立证据，证明i区编码的Ia抗原是mhc相关Ir基因的产物。
A series of experiments were performed to explore the role of complementing major histocompatability 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(a) chains from different haplotypes bearing the serologic specificity Ia.7 was demonstrated by the complementation for high responsiveness to pigeon cytochrome c of F(1) hybrids between low responder B 10.A(4R) (I-A (k)) or B 10.S (I-A(8)) mice and four low responder E(a)- bearing haplotypes. Moreover, this Ir gene function correlated directly with both the ability of antigen-pulsed spleen cells from these same F(1) 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 two-chain Ia antigenic complex, A(e):E(a), bearing the conformational or combinatorial determinant recognized by the monoclonal anti-Ia antibody, Y-17. The B 10.PL strain (H-2(u)), which expresses an Ia.7-positive I-E- subregion-encoded E(a) chain, failed to complement with B10.A(4R) or B10.S mice in the response to pigeon cytochrome c. However, (B10.A(4R) × B10.PL)F(1) and (B10.S × B10.PL)F(1) mice do express A(k)(e):E(u)(a) and A(8)(e):E(u)(a) on their cell surface, although in reduced amounts relative to A(k,s)(e):E(k,d,p,r)(a) complexes found in corresponding F(1) strains. This quantitative difference in Ia antigen expression correlated with a difference in the ability to present pigeon cytochrome c to B 10.A and B 10.S(9R) long-term T cell lines. Thus, (B10.A(4R) × B10.PL)F(1) spleen cells required a 10-fold higher antigen dose to induce the same stimulation as (B10.A(4R) × B10.D2)F(1) spleen cells. In addition, the monoclonal antibody, Y-17, which reacts with A(e):E(a) 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) X B10.PL)F(1) spleen cells than in the presence of (B10.A(4R) X B10.D2)F(1) spleen cells. These functional data, in concert with the biochemical and serological data in the accompanying report, are consistent with the molecular model for Ir gene complementation in which appropriate two-chain Ia molecules function at the antigen-presenting cell (APC) surface as restriction elements. Moreover, they clearly demonstrate that 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. Finally, 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.