Wettstein P J, Colombo M P
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
J Immunol. 1987 Oct 1;139(7):2166-71.
The immunization of C57BL/6 responder mice with spleen cells from H-2-matched BALB.B donors, which differ by multiple non-H-2 histocompatibility (H) antigens, results in the generation of cytotoxic T lymphocytes (CTL) that are specific for only a limited number of immunodominant antigens. Previous analysis of the genes encoding these dominant antigens has not mapped these genes to any of the non-H-2 H loci defined by congenic strains. It would have been expected that the histogenetic techniques employed for congenic strain selection would have preferentially identified the "strongest" H antigens. Therefore, we have investigated the possibility that immunodominant antigens do not belong to the class of non-H-2 H antigens encoded by genes mapping to H loci defined and mapped by congenic strains. The first experiments were aimed at identifying antigens that were expressed by independently derived inbred strains and were cross-reactive with the immunodominant cytotoxic T cell target (CTT-1) antigen of BALB.B. Strong cross-reaction with the C3H.SW (H-2b) strain was observed; the C3H gene encoding this antigen was mapped with BXH recombinant inbred strains. Contrary to the mapping of the CTT-1 gene to chromosome 1 in BALB.B, the C3H gene was shown to map to either chromosome 4 or chromosome 7. This result indicates that identical, or at least extensively cross-reactive, non-H-2 antigens may be encoded by genes mapping to independently segregating loci in different inbred strains. The tissue distribution of immunodominant antigens was approached by determining the reactivity of CTL specific for these antigens with either lymphoid-derived or fibroblast-derived targets. These CTL effectively lysed lymphoblast and lymphoid tumor targets but did not lyse an SV40-transformed fibroblast line that was shown to be efficiently lysed by CTL specific for non-H-2 H antigens defined by congenic strains. Therefore, it was concluded that immunodominant antigens detected by B6 anti-BALB.B CTL have a restricted tissue distribution in comparison to non-H-2 H antigens defined by congenic strains. The implications of these results for our understanding of the origin and heterogeneity of non-H-2 cell-surface antigen recognized by effector T cells are discussed.
用来自H - 2匹配的BALB.B供体的脾细胞对C57BL/6应答小鼠进行免疫，BALB.B与C57BL/6在多个非H - 2组织相容性（H）抗原上存在差异，结果产生了仅对有限数量的免疫显性抗原具有特异性的细胞毒性T淋巴细胞（CTL）。先前对编码这些显性抗原的基因的分析尚未将这些基因定位到由同源近交系定义的任何非H - 2 H位点。人们原本预期用于同源近交系选择的组织发生技术会优先识别出“最强的”H抗原。因此，我们研究了免疫显性抗原不属于由定位到同源近交系定义和定位的H位点的基因所编码的非H - 2 H抗原类别的可能性。最初的实验旨在鉴定由独立衍生的近交系表达且与BALB.B的免疫显性细胞毒性T细胞靶标（CTT - 1）抗原发生交叉反应的抗原。观察到与C3H.SW（H - 2b）品系有强烈交叉反应；编码该抗原的C3H基因通过BXH重组近交系进行定位。与CTT - 1基因在BALB.B中定位到1号染色体相反，C3H基因显示定位到4号染色体或7号染色体。这一结果表明，相同的或至少广泛交叉反应的非H - 2抗原可能由定位到不同近交系中独立分离位点的基因所编码。通过确定针对这些抗原的CTL与淋巴样来源或成纤维细胞来源的靶标的反应性，来研究免疫显性抗原的组织分布。这些CTL有效地裂解了淋巴母细胞和淋巴样肿瘤靶标，但未裂解一个SV40转化的成纤维细胞系，而该细胞系已被证明能被针对同源近交系定义的非H - 2 H抗原的CTL有效裂解。因此，得出结论，与同源近交系定义的非H - 2 H抗原相比，B6抗BALB.B CTL检测到的免疫显性抗原具有受限的组织分布。讨论了这些结果对于我们理解效应T细胞识别的非H - 2细胞表面抗原的起源和异质性的意义。
