T-lymphocyte response to cytochrome c. I. Demonstration of a T-cell heteroclitic proliferative response and identification of a topographic antigenic determinant on pigeon cytochrome c whose immune recognition requires two complementing major histocompatibility complex-linked immune response genes.
T-lymphocyte response to cytochrome c. I. Demonstration of a T-cell heteroclitic proliferative response and identification of a topographic antigenic determinant on pigeon cytochrome c whose immune recognition requires two complementing major histocompatibility complex-linked immune response genes.
复制标题
T淋巴细胞对细胞色素c的反应。 I.在鸽子细胞色素C上的T细胞异晶性增殖反应和鉴定的T细胞杂点增殖反应和鉴定，其免疫识别需要两个补充主要的组织相容性复杂的免疫反应基因。
DOI：
10.1084/jem.150.4.830
复制
发表时间：
1979-10-01
影响因子：
15.3
通讯作者：
Schwartz, R H
中科院分区：
文献类型：
--
作者：
Solinger, A M;Ultee, M E;Margoliash, E;Schwartz, R H
本文研究了家鸽细胞色素c对小鼠T淋巴细胞增殖反应的影响。H-2a和H-2k菌株对该抗原有应答，而H-2b、H-2d、H-2f、H-2 ja、H-2 p、H-2 q、H-2 r、H-2s和H- 2u菌株则低应答或无应答。基因定位表明，两个主要组织相容性复合体（MHC）连锁的Ir基因控制的反应，一个在I-A，另一个在I-E/I-C。在这种反应中识别的主要抗原决定簇通过与物种变体和细胞色素c的溴化氰切割片段的交叉刺激而定位。它被发现是一个地形表面决定簇组成的异亮氨酸取代缬氨酸在残基3，谷氨酰胺取代赖氨酸在残基100和赖氨酸取代谷氨酸在残基104。烟草天蛾细胞色素c在残基100处含有谷氨酰胺，但在残基103处含有末端赖氨酸（靠近谷氨酰胺的一个氨基酸），其刺激鸽子细胞色素c免疫T细胞的效果优于免疫原。这一结果表明，第一次在Ir基因控制下的系统中的功能性T细胞的异型增殖反应。用溴化氰裂解片段免疫表明，只有鸽细胞色素c片段81-104具有免疫原性。该片段引发T细胞增殖反应，其特异性与整个分子引发的T细胞反应的特异性几乎相同，表明100处的谷氨酰胺和104处的赖氨酸形成抗原位点的免疫显性部分。此外，使用两种交叉反应抗原--河蚌细胞色素c和北京鸭或鸡细胞色素c片段（81-104）（每种抗原仅含有两种免疫显性取代中的一种）进行的混合实验表明，对主要抗原决定簇应答的T淋巴细胞包含单个克隆家族，该克隆家族将两种氨基酸识别为同一决定簇的一部分。因此，两个互补的MHC连锁的Ir基因可以控制对单个抗原决定簇的免疫应答。
The T-lymphocyte proliferative response to pigeon cytochrome c was studied in the mouse. H-2a and H-2k strains were responders to this antigen whereas H-2b, H-2d, H-2f, H-2ja, H-2p, H-2q, H-2r, H-2s, and H- 2u strains were low or nonresponders. Genetic mapping demonstrated that two major histocompatibility complex (MHC)-linked Ir genes control the response, one in I-A, the other in I-E/I-C. The major antigenic determinant recognized in this response was localized by cross- stimulations with species variants and cyanogen bromide cleavage fragments of cytochrome c. It was found to be a topographic surface determinant composed of an isoleucine for valine substitution at residue 3, a glutamine for lysine substitution at residue 100 and a lysine for glutamic acid substitution at residue 104. Tobacco hornworm moth cytochrome c, which contains a glutamine at residue 100 but a terminal lysine at residue 103 (one amino acid closer to the glutamine), stimulated pigeon cytochrome c immune T cells better than the immunogen. This result demonstrates for the first time a functional T-cell heteroclitic proliferative response in a system under Ir gene control. Immunization with the cyanogen bromide cleavage fragments revealed that only pigeon cytochrome c fragment 81-104 was immunogenic. This fragment primed for a T-cell proliferative response whose specificity was nearly identical to that of the T-cell response primed for by the whole molecule, suggesting that the glutamine at 100 and the lysine at 104 form the immunodominant portion of the antigenic site. Furthermore, mixing experiments using the two cross-reacting antigens, hippopotamus cytochrome c and Pekin duck or chicken cytochrome c fragment (81-104), each of which contains only one of the two immunodominant substitutions, demonstrated that the T lymphocytes responding to the major antigenic determinant comprise a single family of clones that recognize both amino acids as part of the same determinant. Thus, two complementing MHC-linked Ir genes can control the immune response to a single antigenic determinant.