Hansburg D, Heber-Katz E, Fairwell T, Appella E
J Exp Med. 1983 Jul 1;158(1):25-39. doi: 10.1084/jem.158.1.25.
In previous work (5,6), we have reported studies on a T lymphocyte hybridoma clone and the peritoneal exudate T cells (PETLES) from B10.A(5R) mice primed with the cytochrome c carboxyl terminal peptide (residues 81-103) of the tobacco horn worm moth (Manducca sextus). As expected, since B10.A(5R) is a low responder to pigeon fragment 81-104, it was found that the B10.A(5R) lymphocytes were unable to respond to the pigeon cytochrome c 81-104 fragment presented on syngeneic B10.A(5R) antigen-presenting cells (APC). However, these same T lymphocytes did respond to the pigeon fragment when presented on B10.A APC. Thus, some structural difference between the pigeon and moth peptides had prevented B10.A(5R) APC from effectively presenting the pigeon fragment to moth-primed B10.A(5R) lymphocytes. This structural difference was found to be the deletion of an alanine at position -103 (Ala103) from the pigeon sequence in the moth peptide. Two additional T cell specificities were created by changing residue-99. These T cell populations from the B10.A(5R) showed an identical dependence on the Ala103 deletion when B10.A and B10.A(5R) APC were compared. The relationship of APC-expressed antigen specificity and MHC-linked immune responsiveness differences was also examined. The B10.A(5R) was found to be a high responder to each of three peptides that lack Ala103 but not to the Ala103-containing analogues. B10.A mice, in contrast, respond to both types of peptides. Utilizing allogeneic antigen-presentation to B10.A PETLES by pulsed APC, it was shown that the poor response of the B10.A(5R) to the Ala103-containing peptides was, in two of three cases, not associated with any differences in T cell repertoires but due to two different APC capabilities of B10.A and B10.A(5R). The exception apparently represents a case of T cell repertoire polymorphism between B10.A and B10.A(5R) that can also affect immune responsiveness.
在之前的研究（5,6）中，我们报道了对一种T淋巴细胞杂交瘤克隆以及来自用烟草天蛾（烟草天蛾属）细胞色素c羧基末端肽（第81 - 103位氨基酸残基）免疫的B10.A(5R)小鼠的腹腔渗出液T细胞（PETLES）的研究。正如预期的那样，由于B10.A(5R)对鸽细胞色素c第81 - 104位片段是低反应者，我们发现B10.A(5R)淋巴细胞无法对同基因B10.A(5R)抗原呈递细胞（APC）呈递的鸽细胞色素c第81 - 104位片段产生反应。然而，当这些相同的T淋巴细胞由B10.A APC呈递时，它们确实对鸽细胞色素c片段产生了反应。因此，鸽细胞色素c肽和蛾细胞色素c肽之间的某些结构差异阻止了B10.A(5R) APC有效地将鸽细胞色素c片段呈递给用蛾细胞色素c肽免疫的B10.A(5R)淋巴细胞。发现这种结构差异是蛾细胞色素c肽中相对于鸽细胞色素c序列在第 - 103位（丙氨酸103）缺失了一个丙氨酸。通过改变第99位氨基酸残基又产生了另外两种T细胞特异性。当比较B10.A和B10.A(5R) APC时，来自B10.A(5R)的这些T细胞群体对丙氨酸103缺失表现出相同的依赖性。我们还研究了APC表达的抗原特异性与MHC连锁的免疫反应性差异之间的关系。发现B10.A(5R)对三种不含丙氨酸103的肽中的每一种都是高反应者，但对含丙氨酸103的类似物则不是。相比之下，B10.A小鼠对这两种类型的肽都有反应。通过用脉冲APC对B10.A PETLES进行同种异体抗原呈递，结果表明，在三种情况中的两种情况下，B10.A(5R)对含丙氨酸103的肽反应不佳并非与T细胞库的任何差异有关，而是由于B10.A和B10.A(5R)的两种不同的APC呈递能力。例外情况显然代表了B10.A和B10.A(5R)之间T细胞库多态性的一个例子，这种多态性也会影响免疫反应性。
