Fine specificity of genetic regulation of guinea pig T lymphocyte responses to angiotensin II and related peptides.
Fine specificity of genetic regulation of guinea pig T lymphocyte responses to angiotensin II and related peptides.
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豚鼠T淋巴细胞对血管紧张素II和相关肽的遗传调节的精细特异性。
DOI：
10.1084/jem.153.3.583
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发表时间：
1981-03-01
影响因子：
15.3
通讯作者：
Wilner, G D
中科院分区：
文献类型：
--
作者：
Thomas, D W;Hsieh, K H;Schauster, J L;Wilner, G D
使用各种合成肽类似物和同系物检查豚鼠 T 淋巴细胞对八肽抗原血管紧张素 II (NH(2)-Asp(1)-Arg(2)-Val(3)-Tyr(4)-Ile(5)-His(6)-Pro(7)-Phe(8)-OH; AII）的反应。通过体外 T 细胞增殖反应测定每种肽抗原在品系 2 和品系 13 豚鼠中的免疫原性和抗原性。人们发现，T 细胞对这些肽的反应的遗传控制具有高度特异性，并且能够区分抗原的细微差异。例如，品系 2 豚鼠对 AII 有反应，但对 [Val(5)]-AII 反应较低，而品系 13 动物对 [Val(5)]-AII 有反应，但对 AII 没有反应。本例中的遗传控制涉及Val(5)和Ile(5)之间一个甲基的差异。对于涉及 Tyr(4) 和 Phe(8) 苯环上对位取代的类似物，还观察到品系 2 和品系 13 豚鼠 T 细胞反应性的差异。然而，T 细胞反应的基因调控似乎并不基于单个肽残基。例如，去除 Asp(1) 使品系 13 动物能够对含有 Ile(5) 的类似物产生反应，但消除了对含有 Val(5) 的类似物的反应。因此，第一个和第五个AII残基都参与13株T细胞反应的调节。 Tyr(4) 和 Phe(8) 的取代表明相同的残基可能会改变一种菌株中 T 细胞反应的特异性，并决定另一种菌株中的反应性或无反应性。最引人注目的观察结果之一是，T 细胞对各种 AII 类似物和同源物的反应在 2 株和 13 株豚鼠之间随机波动，并且通常两种品系都不对相同的肽抗原产生反应。这表明菌株 2 和菌株 13 T 细胞反应很少针对相同的抗原决定簇，并且 T 细胞抗原组合多样性通常在这两种菌株之间是排他性的。这些结果针对 Ir 基因控制的特异性以及 Ir 基因功能与 T 细胞抗原识别之间的关系进行了讨论。证据中添加的注释：最近使用新批次的 [Val(5)]-AII 的实验表明，[Val(5)]-AII 免疫株 2 T 细胞对 AII 表现出显着的刺激作用，但对 [Val(5)]-AII 的反应仍然相对较低，如表 I 所示。不同批次的 [Val(5)]-AII 引发 AII 交叉反应的差异目前尚不清楚。
Guinea pig T lymphocyte responses to the octapeptide antigen angiotensin II (NH(2)-Asp(1)-Arg(2)-Val(3)-Tyr(4)-Ile(5)-His(6)-Pro(7)-Phe(8)-OH; AII) were examined using various synthetic peptide analogues and homologues. Each peptide antigen was assessed for immunogenicity and antigenicity in strain 2 and strain 13 guinea pigs as determined by in vitro T cell proliferative responses. The genetic control of T cell responses to these peptides was found to be highly specific and capable of distinguishing subtle differences in the antigens. For example, strain 2 guinea pigs responded to AII and were low responders to [Val(5)]-AII, whereas strain 13 animals responded to [Val(5)]-AII but not to AII. The genetic control in this case involved the difference of one methyl group between Val(5) and Ile(5). Differences in T cell responsiveness by strain 2 and strain 13 guinea pigs were also observed with analogues involving para substitutions on the phenyl ring of Tyr(4) and of Phe(8). However, the genetic regulation of T cell responses did not seem to be based on a single peptide residue. For example, removal of Asp(1) allowed strain 13 animals to respond to the Ile(5)-containing analogue, but eliminated responsiveness to the Val(5)-containing analogue. Thus, the first and fifth AII residues are both involved in the regulation of strain 13 T cell responses. Substitutions for Tyr(4) and Phe(8) suggested that the same residue may serve to alter the specificity of T cell responses in one strain, and determine responsiveness or unresponsiveness in the other strain. One of the most striking observations is that T cell responsiveness to the various AII analogues and homologues randomly fluctuates between strain 2 and strain 13 guinea pigs, and in general neither strain responds to the same peptide antigens. This suggests that strain 2 and strain 13 T cell responses are rarely directed against the same antigenic determinants, and that the T cell antigen-combining diversity is usually exclusive between these two strains. These results are discussed with respect to the specificity of Ir gene control and the relationship between Ir gene function and antigen recognition by T cells. Note added in proof: More recent experiments using a new lot of [Val(5)]- AII have indicated that [Val(5)]-AII-immune strain 2 T cells show significant stimulation with AII but remain relatively low responders with [Val(5)]-AII, as shown in Table I. The difference in priming for cross-reactivity for AII with the different lots of [Val(5)]-AII is at present unknown.