ALLOIMMUNIZATION OF MACACA NEMESTRINA W/ MHC CLASS II ANTIGENS

用未感染的人类细胞免疫的猕猴已经显示出， 保护免受在人类细胞中繁殖的SIV的攻击。 到 确定参与这种保护的潜在抗原，猕猴 用未感染的人细胞（HuT 78/H9）、β-2 微球蛋白和HLA I类和II类蛋白， 这些人类细胞。 虽然所有的猕猴都产生了高抗体 免疫蛋白的滴度，只有猕猴 用II类蛋白（HLA-DR）免疫的小鼠产生了针对II类的抗体。 II和保护免受静脉内病毒攻击。 这些 结果首次证明，用纯化的 细胞蛋白可以保护免受病毒感染（L. 亚瑟等人， J Virol 69：3117-3124，1995）。 与Gaur博士合作， 在猪尾猕猴群体中鉴定出II类等位基因， 纯化的II类DR使用相同的技术，导致 具有相似和不同的HLA DR的猕猴的纯化 II类等位基因（由Gaur博士确定）将用 然后用在淋巴细胞中生长的SIVMne攻击 来自纯化II类抗原的动物。 这些 研究将进一步探讨II类抗体是否与 在同种免疫方案中具有免受感染的保护，并且可以 帮助解释为什么在某些群体中对感染有抵抗力 （例如冈比亚的妓女）。 这项研究的结果可能 也适用于艾滋病疫苗的设计。 四只猕猴被用于 一滴攻击病毒 两只猕猴分别得到10-3 1998年8月静脉注射10-4 TCID。 1998年11月， 其余6只猕猴开始DR免疫方案。 资助NIH 赠款RR 00166和SAIC（科学应用国际公司） 授予97 CYS 0192 A。

Macaques immunized with uninfected human cells have been shown to be protected from challenge with SIV propagated in human cells. To identify the potential antigens involved in this protection, macaques were immunized with uninfected human cells (HuT 78/H9), beta-2 microglobulin, and HLA Class I and Class II proteins purified from these human cells. Although all macaques developed high antibody titers to the proteins with which they were immunized, only macaques immunized with Class II protein (HLA-DR) developed antibodies to Class II and were protected from an intravenous virus challenge. These results were the first demonstration that immunization with a purified cellular protein can protect from virus infection (L. Arthur et al., J Virol 69:3117-3124, 1995). In collaboration with Dr. Gaur we identified class II alleles in the pig-tailed macaque colony and purified class II DR using the same techniques that lead to the purification of HLA DR. Macaques that share s imilar and distinct class II alleles (as determined by Dr. Gaur) will be immunized with this purified DR and then challenged with SIVMne grown in lymphocytes from the animal from which the class II antigen was purified. These studies will further address whether antibodies to class II correlate with protection from infection in an alloimmunization regimen, and may help explain why there is resistance to infection in some cohorts (prostitutes in Gambia, for example). The results of this study may also be applicable to AIDS vaccine design. Four macaques were used in a titration of the challenge virus. Two macaques each received 10-3 and 10-4 TCID intravenously in August 1998. In November 1998 the remaining 6 macaques began the DR immunization protocol. FUNDING NIH grant RR00166 and SAIC (Science Applications International Corp.) grant 97CYS0192A.