Deficient antigen processing of a protein quaternary structure can be overcome by receptor‐mediated uptake
Deficient antigen processing of a protein quaternary structure can be overcome by receptor‐mediated uptake
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蛋白质四级结构的抗原加工缺陷可以通过受体介导的摄取来克服
DOI：
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发表时间：
1993
影响因子：
5.4
通讯作者：
D. Bellet
中科院分区：
文献类型：
--
作者：
N. Rouas;F. Housseau;J. Bidart;C. Bonnerot;Sebastien Amigorena;J. Guillet;D. Bellet
人绒毛膜促性腺激素(HCG)是由非共价相关的α(hCG-α)和β(hCG-β)亚基组成的二聚体。这种分子被用来研究受体介导的摄取是否影响蛋白质四级结构的呈现。未诱导的脾细胞和B细胞淋巴瘤对hCG-αT细胞杂交瘤只能表达游离的(hCG-α)而不能表达结合的(HCG)α亚基，而hCG-α诱导的淋巴结细胞(LNC)对hCG-α和hCG均有反应。由于抗原(Ag)特异性抗原提呈细胞(APC)存在于hCG-α诱导的LNC群体中，可能是潜在有效的hCG呈递细胞，我们通过MiG和FcγR研究了特异性Ag捕获在hCG和hCG-a加工和呈递给HAG 5过程中的作用。HAG 5是针对hCG-α免疫优势区(氨基酸61-81)的T细胞杂交瘤。结果表明，只有具有识别hCG-α和hCG的膜免疫球蛋白的B细胞，并且存在于hCG-α诱导的小鼠体内，才能非常有效地呈现游离和结合的α亚基。利用FcγRII-B2基因转染的B细胞株，分析FcR介导的摄取作用，以呈现α或hCG免疫复合物。我们发现，hCG-α和hCG呈现出同样好的效果，无论每个抗体与hCG或其α亚基的抗原结合部位。利用hCG-βT细胞杂交瘤HBG 6，我们对FcγRII-B2细胞株进行了类似的实验，确定hCG呈递给HBG 6的增强作用与HAG 5相似。然后进行动力学实验，以考察FCR摄取Ag对加工的影响。结果表明，摄取途径显著影响αT细胞决定簇在αβ二聚体中的表达。此外，用蛋白质合成抑制剂放线菌亚胺处理，只会削弱APC呈递特定捕获的Ag的能力。因此，特异性捕获的Ag的处理途径可能不同于用于处理非特异性捕获的Ag的途径。这一观察可能解释了为什么受体增强的摄取绕过了hCG四级结构的低效处理，并在呈现α和βT细胞特异性方面实现了类似的效率。这些发现为寡聚体分子的抗原性提供了新的见解，无论抗原捕获是否具有特异性，寡聚体分子的抗原性都会发生改变。
Human chorionic gonadotropin (hCG) is a dimer of non‐covalently associated alpha (hCG‐α) and beta (hCG‐β) subunits. This molecule was used to study whether receptor‐mediated uptake influences the presentation of a protein quaternary structure. Unprimed splenocytes and a B cell lymphoma were capable of presenting only the free (hCG‐α) but not the combined (hCG) α subunit to hCG‐α T cell hybridomas, while hCG‐α‐primed lymph node cells (LNC) responded to both hCG‐α and hCG. As antigen (Ag)‐specific antigen‐presenting cells (APC) present in the hCG‐α‐primed LNC population may be potentially effective for presenting hCG, we investigated the role of specific Ag capture, through mIg and FcγR, in the processing and presentation of hCG and hCG‐a to HAG 5, a T cell hybridoma directed against the immunodominant region (amino acids 61‐81) of hCG‐α. Results showed that only B cells bearing membrane immunoglobulin capable of recognizing hCG‐α and hCG, and present in hCG‐α‐primed mice, were extremely effective in presenting the free as well as the combined a subunit. The effect of FcR‐mediated uptake was analyzed using a B cell line transfected with the FcγRII‐B2 gene to present immune complexes of either hCG‐α or hCG. We found that hCG‐α and hCG were presented equally well, whatever the Ag‐binding site of each antibody to hCG or its a subunit. Using HBG 6, an hCG‐β Tcell hybridoma, we performed similar experiments with the FcγRII‐B2 cell line and determined that the potentiation of hCG presentation to HBG 6 was similar to that observed with HAG 5. Then kinetic experiments were performed to examine the effect of Ag uptake through FcR on processing. Results demonstrated that the uptake pathway drastically influenced the expression of α T cell determinants in the αβ dimer. In addition, treatment with cycloheximide, a protein synthesis inhibitor, only impaired the ability of APC to present specifically captured Ag. Thus, the processing pathway for specifically captured Ag might be different from the pathway used to process nonspecifically captured Ag. This observation might explain why receptor‐enhanced uptake bypasses the inefficient processing of the hCG quaternary structure and enables similar efficiency in the presentation of α and β T cell specificities. These findings provide new insight into the antigenicity of oligomeric molecules, which is modified whether antigen capture is specific or not.
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受体介导的抗原递送至巨噬细胞。
DOI：
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发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chu,CT;Pizzo,SV
通讯作者：
Pizzo,SV
影响因子：
4.4
作者：
R. Chesnut;H. Grey
通讯作者：
R. Chesnut;H. Grey
使用人 Fc γ 受体（单核细胞/巨噬细胞）特异性免疫原增强抗原呈递。
DOI：
--
发表时间：
1992
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gosselin,EJ;Wardwell,K;Gosselin,DR;Alter,N;Fisher,JL;Guyre,PM
通讯作者：
Guyre,PM
人绒毛膜促性腺激素β亚基上的单克隆抗体识别的拓扑抗原决定簇。
DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bidart,JM;Troalen,F;Salesse,R;Bousfield,GR;Bohuon,CJ;Bellet,DH
通讯作者：
Bellet,DH
人绒毛膜促性腺激素α亚基的抗原决定簇。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bidart,JM;Troalen,F;Bousfield,GR;Birken,S;Bellet,DH
通讯作者：
Bellet,DH