de Waal L P, de Hoop J, Stukart M J, Gleichmann H, Melvold R W, Melief C J
J Immunol. 1983 Feb;130(2):655-60.
The B6.C-H-2bm12 (bm12), H-2 I-Ab mutant, originated in the C57BL/6 (B6, H-2b) strain, is a nonresponder to the male antigen H-Y in both T cell proliferation and cytotoxic T lymphocyte (CTL) responses. Defective H-Y presentation by bm12-adherent cells, as a cause of the CTL nonresponsiveness, can be excluded, because 1) CTL from primed responder/nonresponder F1 female mice (B6/bm12 F1) were activated by H-Y antigen on antigen-presenting cells (apc) from either parent; 2) T cells from primed nonresponder bm12 females did not generate CTL to H-Y presented by responder B6 apc, but conversely, CTL from B6 females could be activated by antigen on bm12 apc; and 3) adherent cell-depletion experiments indicated that male adherent cells are necessary for generation of optimal H-Y-specific CTL responses, male adherent bm12 cells being equally as efficient as male adherent B6 cells in presentation to F1 T cells. The need for T helper cell activation by H-Y-presenting adherent cells during secondary in vitro restimulation can be circumvented by interleukin 2 (IL 2), because IL 2 completely restored the H-Y-specific CTL response of B6/bm12 F1 cells in cultures depleted of adherent cells. However, addition of IL 2 during in vitro restimulation of bm12 cells did not result in an H-Y-specific CTL response, indicating that H-Y-specific, I-A-restricted T helper cells are probably needed in vivo during priming for the generation of sufficient numbers of Db-restricted CTL memory cells. The data are compatible with the concept that H-Y antigen is presented in the context of the I-A alpha, beta molecule on the surface of adherent cells to T helper cells and in the context of the Db molecule on the surface of nonadherent as well as adherent cells to CTL precursors. The most likely explanation for the difference in H-Y response between B6 and bm12 include positive selection of the responder phenotype by the I-Ab alpha, beta molecule of the B6 strain or generation of suppressor T cells in the bm12 strain.
B6.C-H-2bm12（bm12），即H-2 I-Ab突变体，起源于C57BL/6（B6，H-2b）品系，在T细胞增殖和细胞毒性T淋巴细胞（CTL）反应中对雄性抗原H-Y均无反应。bm12贴壁细胞对H-Y的呈递缺陷作为CTL无反应的原因可以排除，因为：1）来自致敏的反应者/无反应者F1雌性小鼠（B6/bm12 F1）的CTL被来自任一亲本的抗原呈递细胞（APC）上的H-Y抗原激活；2）来自致敏的无反应者bm12雌性小鼠的T细胞不会对反应者B6 APC呈递的H-Y产生CTL，但相反，来自B6雌性小鼠的CTL可被bm12 APC上的抗原激活；3）贴壁细胞去除实验表明雄性贴壁细胞对于产生最佳的H-Y特异性CTL反应是必需的，雄性贴壁bm12细胞在向F1 T细胞呈递方面与雄性贴壁B6细胞同样有效。在体外二次再刺激期间，通过白细胞介素2（IL-2）可以规避由呈递H-Y的贴壁细胞激活T辅助细胞的需求，因为IL-2完全恢复了在去除贴壁细胞的培养物中B6/bm12 F1细胞的H-Y特异性CTL反应。然而，在体外再刺激bm12细胞期间添加IL-2并未导致H-Y特异性CTL反应，这表明在体内启动过程中可能需要H-Y特异性、I-A限制的T辅助细胞来产生足够数量的Db限制的CTL记忆细胞。这些数据与以下概念相符，即H-Y抗原在贴壁细胞表面的I-Aα、β分子背景下呈递给T辅助细胞，并在非贴壁细胞以及贴壁细胞表面的Db分子背景下呈递给CTL前体。B6和bm12之间H-Y反应差异的最可能解释包括B6品系的I-Abα、β分子对反应者表型的阳性选择或bm12品系中抑制性T细胞的产生。
