Hodes R J, Hathcock K S, Singer A
J Exp Med. 1980 Dec 1;152(6):1779-94. doi: 10.1084/jem.152.6.1779.
The functional role of cell surface Ia antigens has been studied for in vitro antibody responses, using as a probe the ability of anti-Ia reagents to inhibit these responses. A hybridoma monoclonal anti-Ia reagent specific for a product of I-Ak (Ia.17) profoundly inhibited in vitro antibody responses to TNP-KLH by spleen cells of the I-Ak but not I-Ab haplotype. This inhibition by anti-I-Ak product, but not by interaction with T or B cell product, in spite of the fact that functional B cells as well as accessory cells could be shown to express the determinant detected by this hybridoma reagent. These results suggest that the Ia expressed by accessory cells in of unique functional importance in these responses. To further characterize the function of Ia antigens in this response system, the mechanism of anti-I-Ak inhibition was determined. The inhibition resulting from interaction of anti-I-Ak with accessory cell Ia was not mediated by nonspecific suppressor cells, nor was there nonspecific interference with accessory cell function as a result of the binding of anti-Ia antibody. The relationship between anti-Ia inhibition and T helper cell recognition of self determinations on accessory cells was analyzed using T cells from radiation bone marrow chimeras. It was demonstrated that (B10 X B10.A)F1 leads to B10 (F1 leads to B10) chimera T cells were able to cooperate with B10 (H-2b and I-Ab) but not B10.A (H-2a and I-Ak) accessory cells for responses to TNP-KLH; F1 leads to B10.A T cells were able to cooperate with B10.A but not B10 accessory cells; and both chimera populations were able to cooperate with (B10 X B10.A)F1 (F1) accessory cells. Monoclonal anti-I-Ak inhibited the cooperation of F1 leads to B10.A T cells with the same F1 accessory cells. Thus, inhibition by anti-I-Ak is dependent upon active helper T cell recognition of I-Ak-encoded determinants expressed on accessory cells. These findings demonstrate that T cells recognize self Ia determinants expressed on accessory cells, and that such recognition is required for the generation of T cell-dependent antibody responses.
利用抗Ia试剂抑制体外抗体反应的能力作为探针，对细胞表面Ia抗原的功能作用进行了研究。一种针对I-Ak产物（Ia.17）的杂交瘤单克隆抗Ia试剂，能显著抑制I-Ak单倍型脾细胞对TNP-KLH的体外抗体反应，但对I-Ab单倍型的脾细胞无此作用。尽管功能性B细胞以及辅助细胞都能表达这种杂交瘤试剂所检测到的决定簇，但抗I-Ak产物的这种抑制作用并非通过与T或B细胞产物相互作用产生。这些结果表明，辅助细胞所表达的Ia在这些反应中具有独特的功能重要性。为了进一步阐明Ia抗原在该反应系统中的功能，确定了抗I-Ak抑制作用的机制。抗I-Ak与辅助细胞Ia相互作用所导致的抑制作用，并非由非特异性抑制细胞介导，抗Ia抗体的结合也不会对辅助细胞功能产生非特异性干扰。利用辐射骨髓嵌合体的T细胞，分析了抗Ia抑制作用与辅助细胞上自身决定簇的T辅助细胞识别之间的关系。结果表明，（B10×B10.A）F1→B10（F1→B10）嵌合体的T细胞能够与B10（H-2b和I-Ab）辅助细胞协作，对TNP-KLH产生反应，但不能与B10.A（H-2a和I-Ak）辅助细胞协作；F1→B10.A的T细胞能够与B10.A辅助细胞协作，但不能与B10辅助细胞协作；并且这两种嵌合体群体都能够与（B10×B10.A）F1（F1）辅助细胞协作。单克隆抗I-Ak抑制了F1→B10.A的T细胞与相同F1辅助细胞之间的协作。因此，抗I-Ak的抑制作用依赖于辅助细胞上表达的I-Ak编码决定簇的活性辅助性T细胞识别。这些发现表明，T细胞能够识别辅助细胞上表达的自身Ia决定簇，并且这种识别是产生T细胞依赖性抗体反应所必需的。
