von Bonin A, Plaga S, Ruh H, Hebbelmann S, Pflugfelder U, Martin S, Weltzien H U
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Eur J Immunol. 1996 Jan;26(1):179-86. doi: 10.1002/eji.1830260128.
Hapten-specific T cell responses are responsible for chemically induced immune disorders. However, the molecular details of hapten interactions with T cell receptors (TCR) are poorly understood. Recent studies of trinitrophenyl (TNP)-specific responses revealed major histocompatibility complex-associated TNP-peptides as dominant epitopes for CD8+ and CD4+ T cells. The present study is based on the observation that two H-2Kb/TNP-specific CTL clones (II/7 and III/1), differing exclusively in two amino acids of their TCR alpha chains, also differed in their carrier specificities for various TNP-peptides. The genes of the two alpha chains and the common beta chain were cloned into expression vectors. Transfection of the TCR alpha chain of clone III/1 into a hybridoma of clone II/7 also transferred the fine specificity of clone III/1, indicating that the small alpha chain variations were indeed responsible for the different carrier specificities. Point mutations bridging the difference between the alpha chains of clones II/7 and III/1 and functional studies of the respective TCR alpha beta transfectants into a TCR-negative hybridoma revealed an unexpected result: the two receptors did not represent examples of structural complementarity for different sets of hapten-peptide conjugates; rather, they resembled two structures of principally similar specificity but of significantly different overall affinity. This was demonstrated more directly by comparing the fine specificities of III/1 transfectants expressing or not expressing the co-receptor CD8: the CD8-negative III/1 transfectant assumed a specificity pattern indistinguishable from that of a CD8-expressing, II/7-derived transfectant. Hence, comparable alterations of antigen recognition may be induced either by subtle TCR alterations or by removal of CD8, i.e. by the presence or absence of a non-polymorphic adhesion molecule.
半抗原特异性T细胞反应是化学诱导免疫紊乱的原因。然而，对半抗原与T细胞受体（TCR）相互作用的分子细节了解甚少。最近对三硝基苯基（TNP）特异性反应的研究表明，主要组织相容性复合体相关的TNP肽是CD8 +和CD4 + T细胞的主要表位。本研究基于以下观察结果：两个H-2Kb/TNP特异性CTL克隆（II/7和III/1），其TCRα链仅在两个氨基酸上不同，它们对各种TNP肽的载体特异性也不同。将两条α链和共同的β链的基因克隆到表达载体中。将克隆III/1的TCRα链转染到克隆II/7的杂交瘤中，也转移了克隆III/1的精细特异性，表明α链的微小变化确实是不同载体特异性的原因。连接克隆II/7和III/1的α链之间差异的点突变以及将各自的TCRαβ转染体导入TCR阴性杂交瘤的功能研究揭示了一个意外的结果：这两种受体并不是不同组半抗原 - 肽缀合物的结构互补性的例子；相反，它们类似于两种主要具有相似特异性但总体亲和力明显不同的结构。通过比较表达或不表达共受体CD8的III/1转染体的精细特异性，更直接地证明了这一点：CD8阴性的III/1转染体呈现出与表达CD8的II/7衍生转染体无法区分的特异性模式。因此，抗原识别的可比改变可能是由TCR的细微改变或CD8的去除引起的，即由非多态性粘附分子的存在或不存在引起。
