Thomas D W, Hsieh K H, Schauster J L, Mudd M S, Wilner G D
J Exp Med. 1980 Sep 1;152(3):620-32. doi: 10.1084/jem.152.3.620.
Guinea pig T lymphocyte responses to a decapeptide antigen (NH1-Asp5-Ans6-Glu7-Glu8-Gly9-Phe10-Phe11-Ser12-Ala13-Arg14-OH) of human fibrinopeptide B (hFPB) were examined using various synthetic peptide analogues containing single residue substitutions. Each analogue was examined for antigenicity as determined by an in vitro proliferative responses of hFPN-immune strain 2 guinae pig T cells. In addition, both strain 2 and strain 13 animals were immunized with each analogue and immunogenicity assessed by in vitro T cell-proliferative responses with the homologous immunizing analogue and the parent peptide. Replacement of arginine14 with lysine formed an immunogenic analogue which showed no antigenic cross-reactivity with the native peptide in strain 2 T cell responses. In addition, substitution of arginine14 with blocked lysine again produced a unique immunogenic analogue that showed little or no antigenic identity with the intact lysine analogue or the native peptide. In similar fashion, substitution of resideu phenylalanie10 with tyrosine or Phe(4-NO2) created unique immunogenic analogues with little or no antigenic identity to the native peptide with strain 2 T cells. By contrast, replacement of phenylalanine11 with either tyrosine or Phe(4-NO2) resulted in analogues with a total loss of immunogenicity and antigenicity in strain 2 T cell responses. An analogue in which glutamic acid7,8 were replaced with glutamine retained a small degree of antigenicity with hFPB-immune T cells, but T cells from strain 2 animals immunized with the Gln analogue responded only marginally to the Gln analogue while producing good proliferative responses with the native peptide. On the other hand, an analogue in which asparatic acid5 was replaced with asparagine retained most of the antigenic identity with hFPB for strain 2 T cell responses. None of thee analogues were immunogenic for strain 13 guinea pigs. These observations are discussed with respect to the contribution of each substituted residue to T cell respones, mechanism of Ir gene function, and a model for T cell recognition of small peptide antigens.
使用含有单个残基取代的各种合成肽类似物，检测了豚鼠T淋巴细胞对人纤维蛋白肽B（hFPB）的十肽抗原（NH1 - Asp5 - Ans6 - Glu7 - Glu8 - Gly9 - Phe10 - Phe11 - Ser12 - Ala13 - Arg14 - OH）的反应。通过hFPN免疫的2号品系豚鼠T细胞的体外增殖反应，检测每种类似物的抗原性。此外，用每种类似物对2号品系和13号品系动物进行免疫，并通过用同源免疫类似物和亲本肽进行体外T细胞增殖反应来评估免疫原性。用赖氨酸取代精氨酸14形成了一种免疫原性类似物，在2号品系T细胞反应中，该类似物与天然肽没有抗原交叉反应。此外，用封闭的赖氨酸取代精氨酸14再次产生了一种独特的免疫原性类似物，该类似物与完整的赖氨酸类似物或天然肽几乎没有或没有抗原同一性。以类似的方式，用酪氨酸或苯丙氨酸（4 - NO2）取代苯丙氨酸10残基，产生了独特的免疫原性类似物，在2号品系T细胞中与天然肽几乎没有或没有抗原同一性。相比之下，用酪氨酸或苯丙氨酸（4 - NO2）取代苯丙氨酸11导致类似物在2号品系T细胞反应中完全丧失免疫原性和抗原性。用谷氨酰胺取代谷氨酸7、8的类似物与hFPB免疫的T细胞保留了一定程度的抗原性，但用谷氨酰胺类似物免疫的2号品系动物的T细胞对谷氨酰胺类似物的反应仅为轻微反应，而对天然肽产生良好的增殖反应。另一方面，用天冬酰胺取代天冬氨酸5的类似物在2号品系T细胞反应中与hFPB保留了大部分抗原同一性。这些类似物对13号品系豚鼠均无免疫原性。针对每个取代残基对T细胞反应的贡献、Ir基因功能机制以及小肽抗原的T细胞识别模型，对这些观察结果进行了讨论。
