IMMUNOBIO OF H-40, AN IGH-LINKED HISTOCOMPATIBILITY GENE

H-40，一种与IgH基因连锁的小鼠组织相容性(H)基因， 控制表面表达的次要H抗原的表达 免疫球蛋白阳性(SIG+)脾淋巴细胞和SIGM+B细胞 肿瘤。它在BALB/c(Igha/H-40a)B细胞白血病上的存在， BCL1在Ighb/H-40b同源动物中引起排斥反应 产生抗H-40a细胞毒性T淋巴细胞(CTL)。 由于H-40的表达仅限于Sig+细胞，这可能是由于 H-40与免疫球蛋白的相互作用。我们将通过以下方式测试这一可能性 通过：(1)封顶Sig；(2)诱导 对Sig细胞的诱导分化；(3)将Mu基因导入Sig细胞。 细胞。我们将使用重组近交系进一步绘制H-40的图谱， 确定其多态，并定义其与其他 与IgH相关的基因。 荷瘤骨的移植物抗宿主(GVH)反应 骨髓移植受者有时与一种抗肿瘤药物有关 效果。解释这种移植物抗白血病效应的一种可能性是 捐献者骨髓接种中包含的效应器T细胞， 识别肿瘤表达的宿主次要H-同种异体抗原。我们已经展示了 这种可能性不会发生在H-40抗原上。因此， 亚致死性照射的H-40b动物携带H-40a肿瘤可以 通过过继转移同基因H-40b来保护其免受致死作用 抗H-40a效应性T细胞。然而，这些效应器T细胞并不 保护亚致死剂量的H-40a接受者免受相同H-40a的伤害 肿瘤。抗H-40a T细胞不能显示抗肿瘤活性 在H-40a宿主中的作用可能是由于：(1)H-40a在宿主中的表达 转移肿瘤效应细胞的正常组织；或(2) 由于宿主供体中的GVH反应，T细胞活跃 被压制了。我们将进行实验来区分这两者 可能性。 GVH反应诱导抗白血病作用的另一种机制 在荷瘤动物中是通过激活耐辐射宿主 抗肿瘤细胞。这种可能性将通过确定老鼠是否， 它们已被启动，以包含特定于 同基因肿瘤，在它们所在的条件下表现出肿瘤耐药性 骨髓移植后行GVH。这些细胞负责 这种抵抗力，无论是捐赠者还是宿主，都将被确定。(AG)

H-40, a murine histocompatibility (H)-gene linked to the Igh locus, controls the expression of a minor H antigen expressed on surface immunoglobulin positive (sIg+) splenic lymphoblasts and sIgM+ B-cell tumors. Its presence on the BALB/c (Igha/H-40a) B-cell leukemia, BCL1, causes its rejection in Ighb/H-40b congenic animals and the generation of anti-H-40a cytotoxic T lymphocytes (CTL). Since the expression of H-40 is limited to sIg+ cells, this could be due to interaction between H-40 and Ig. We will test this possibility by modulating expression either by: (1) capping sIg; (2) inducing differentiation on sIg- cells; or (3) transfecting mu genes into sIg- cells. We will use recombinant inbred strains to further map H-40, determine its polymorphism, and define its relationship with other Igh-linked genes. A graft-versus-host (GVH) response in tumor-bearing bone marrow-transplanted recipients is sometimes associated with an antitumor effect. One possibility to explain this graft-versus-leukemia effect is that effector T cells, contained in the donor bone marrow inoculum, recognize a host minor H-alloantigen expressed by the tumor. We have shown that this possibility does not occur with the H-40 antigen. Thus, sublethally irradiated H-40b animals bearing an H-40a tumor can be protected from its lethal effects by adoptive transfer of syngeneic H-40b anti-H-40a effector T cells. However, these effector T cells do not protect sublethally irradiated H-40a recipients from the same H-40a tumor. The inability of anti-H-40a T cells to display an antitumor effect in H-40a hosts could be due to: (1) the expression of H-40a on normal tissues which diverts the effector cells from the tumor; or (2) because of a GVH reaction in the host donor T cells are actively suppressed. Experiments will be performed to distinguish between these two possibilities. Another mechanism by which a GVH response could induce anti-leukemic effect in tumor-bearing animals is by activating radiation-resistance host antitumor cells. This possibility will be tested by determining if mice, which have been primed so as to contain CTL precursors specific for a syngeneic tumor, display tumor resistance under conditions where they are bone marrow transplanted and subjected to GVH. The cells responsible for this resistance, both donor and host, will be determined. (AG)