Doherty P C, Bennink J R
J Exp Med. 1979 Nov 1;150(5):1187-94. doi: 10.1084/jem.150.5.1187.
Negatively selected H-2K(b)D(b) TDL can be induced to respond strongly to vaccinia virus presented in the context of both H-2K(k) and H-2D(b) when stimulated in irradiated H-2K(k)D(b) recipients. Addition of excess (H- 2K(k)D(b) x H-2K(b)D(b))F1 TDL, which are low responders to H-2D(b)-vaccinia virus, does not obviously suppress the reactivity pattern of the H-2K(b)D(b) T cells. However, lymphocytes from chimeras made by reconstituting H- 2K(b)D(b) mice with (H-2K(k)D(k) x H-2K(b)D(b))F(l) bone marrow cells make little, if any, cytotoxic T-cell response to vaccinia virus when sensitized in H-2K(k)D(b) recipients. We have thus documented one instance where the responder phenotype of T ceils from an F(l) {arrow} parent chimera is not equivalent to that associated with the H-2 type of the parental thymus. Lymphocytes from both the chimera and the H-2K(b)D(b) parent (after negative selection) are tolerant to the H-2K(k) and I-A(k) alloantigens encountered in the recipient, but the chimera T cells are also defective in their response to a neoantigen (vaccinia virus) presented in the context of H-2K(k) which the parental T cells invariably recognize. It is thus possible that at least part of the phenomenology associated with the F(l) {arrow} parent radiation chimeras reflects deletion of repertoire in the context of H-2 antigens present during thymocyte ontogeny on other than radiation-resistant thymic epithelium.
经阴性选择的H-2K(b)D(b) TDL在受照射的H-2K(k)D(b)受体中受到刺激时,可被诱导对在H-2K(k)和H-2D(b)背景下呈递的痘苗病毒产生强烈反应。添加过量的(H-2K(k)D(b)×H-2K(b)D(b))F1 TDL(其对H-2D(b)-痘苗病毒反应较弱),并不会明显抑制H-2K(b)D(b) T细胞的反应模式。然而,用(H-2K(k)D(k)×H-2K(b)D(b))F1骨髓细胞重建H-2K(b)D(b)小鼠所产生的嵌合体的淋巴细胞,在H-2K(k)D(b)受体中致敏时,对痘苗病毒几乎不产生细胞毒性T细胞反应(如果有反应的话也很微弱)。因此,我们记录了一个实例,即来自F1→亲代嵌合体的T细胞的反应表型与亲代胸腺的H-2类型所关联的表型并不等同。嵌合体和亲代H-2K(b)D(b)(经阴性选择后)的淋巴细胞对受体中遇到的H-2K(k)和I-A(k)同种异体抗原均具有耐受性,但嵌合体T细胞对在H-2K(k)背景下呈递的新抗原(痘苗病毒)的反应也存在缺陷,而亲代T细胞总能识别该新抗原。因此,与F1→亲代辐射嵌合体相关的至少部分现象学可能反映了在胸腺细胞个体发育过程中,除了抗辐射胸腺上皮外,在其他H-2抗原背景下 repertoire 的缺失。