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

H-40，与Igh基因座连锁的鼠组织相容性（H）基因， 控制在表面表达的次要H抗原的表达， 免疫球蛋白阳性（sIg+脾淋巴母细胞和sIgM+ b细胞 肿瘤的 它在BALB/c上的存在（Igh一/H-40一B细胞白血病， Bcl1，导致其在Igh中的排斥B/H-40B 同类动物和 抗H-40抗体的产生一 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和IG之间的相互作用。 我们将测试这种可能性， 通过以下方式调节表达：（1）加帽sIg;（2）诱导 sIg分化- （3）将mu基因导入sIg中- 细胞 我们将使用重组近交系进一步绘制H-40图谱， 确定它的多态性，并定义它与其他 免疫球蛋白连锁基因 荷瘤骨的移植物抗宿主（GVH）反应 骨髓移植受者有时与抗肿瘤药物有关。 效果 解释这种移植物抗白血病效应的一种可能性是 包括在供体骨髓接种物中的效应T细胞， 识别由肿瘤表达的宿主次要H-同种异体抗原。 我们已经表明 H-40抗原不存在这种可能性。 因此，在本发明中， 亚致死剂量辐照的H-40B 携带H-40的动物一 肿瘤可以是 通过过继转移同系H-40，B 抗H-40一 效应T细胞 然而，这些效应T细胞不 保护受到亚致死辐射的H-40一 同一H-40的接收者一 肿瘤 抗H-40抗体一 T细胞展示抗肿瘤 在H-40中的作用一 可能是由于：（1）H-40的表达一 对 使效应细胞从肿瘤转移的正常组织;或（2） 由于宿主供体T细胞中的GVH反应， 抑制 将进行实验以区分这两者 可能性 GVH应答可诱导抗白血病作用的另一种机制 是通过激活抗辐射宿主 抗肿瘤细胞 这种可能性将通过确定小鼠， 其已被引发以含有特异于 同基因肿瘤，在它们所处的条件下显示肿瘤抗性， 移植骨髓并进行GVH。 细胞负责 将确定供体和宿主的这种抗性。 （非洲集团）

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)