Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization.

Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization.
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通过体内肽免疫诱导卵蛋白特异性细胞毒性T细胞。

DOI:
10.1084/jem.169.3.603
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发表时间:
1989-03-01
影响因子:
15.3
通讯作者:
BEVAN, MJ
BEVAN, MJ
中科院分区:
医学1区
文献类型:
--
作者:
CARBONE, FR;BEVAN, MJ

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CTL识别与MHC编码的I类分子相关的加工过的外来抗原的多肽形式,通常针对内源性合成的“细胞抗原”,如由病毒感染的细胞表达的抗原。体外研究表明,外源性小肽可以直接与细胞表面的I类分子结合,并模拟细胞内加工和递呈所产生的靶复合体。最近,我们用OVA基因转染的同基因肿瘤株免疫C57BL/6小鼠,产生了OVA特异的、H-2kb限制性的CTL。CTL能识别转OVA基因的E.G7-OVA和合成肽OVA258-276,但不能识别天然蛋白。我们推测,考虑到体外观察到的直接多肽/I类结合的可能性,OVA258-276在体内启动后可能会诱导CTL。然而,我们发现情况并非如此。OVA258-276和长至OVA242-276和OVA242-285的多肽都能在体外形成靶复合体,在静脉注射后不能有效地启动E.G7-OVA特异性CTL反应。对于天然卵子和变性卵子来说也是如此。与这些结果相反,合成的OVA229-276多肽对应于OVA部分胰酶消化的多肽,静脉注射后能有效地在体内启动C57BL/6小鼠。这种多肽诱导的CTL似乎与用内源性产生OVA的同源细胞免疫的动物的CTL相同。这些结果从不同的I类和II类抗原提呈途径以及只有某些外源抗原进入细胞质I类途径的能力方面进行了讨论。
CTL recognize peptide forms of processed, foreign antigens in association with class I molecules encoded by the MHC and are usually directed against endogenously synthesized "cellular antigens," such as those expressed by virus-infected cells. In vitro studies have shown that small exogenous peptides can directly associate with class I molecules on the cell surface and mimic the target complex derived by intracellular processing and presentation. We have recently generated OVA-specific, H-2Kb-restricted CTL by immunizing C57BL/6 mice with a syngeneic tumor line transfected with the OVA cDNA. The CTL recognize the OVA transfectant E.G7-OVA and the synthetic peptide OVA258-276, but fail to recognize the native protein. We reasoned that given the potential for direct peptide/class I association observed in vitro, OVA258-276 may induce CTL after in vivo priming. However, we found that this is not the case. OVA258-276 and peptides of increasing lengths up to OVA242-276 and OVA242-285, which are all able to form the target complex in vitro, are inefficient at priming E.G7-OVA-specific CTL responses after intravenous injection. This is also true for both native and denatured OVA. In contrast to these results the synthetic peptide OVA229-276 corresponding to a peptide in a partial tryptic digestion of OVA can efficiently prime C57BL/6 mice in vivo after intravenous injection. This peptide elicits CTL that appear identical to those derived from animals immunized with syngeneic cells producing OVA endogenously. These results are discussed in terms of separate class I and class II antigen presentation pathways and the ability of only certain, exogenous antigens to enter the cytoplasmic, class I pathway.
DOI: 10.1016/0092-8674(85)90103-5
发表时间: 1985-01-01
期刊: CELL
影响因子: 64.5
作者:
TOWNSEND, ARM;GOTCH, FM;DAVEY, J
通讯作者: DAVEY, J
DOI: 10.1126/science.3158076
发表时间: 1985-01-01
期刊: SCIENCE
影响因子: 56.9
作者:
BRIGGS, MS;GIERASCH, LM;DEGRADO, WF
通讯作者: DEGRADO, WF
DOI: 10.1084/jem.164.5.1397
发表时间: 1986-11-01
期刊: The Journal of experimental medicine
影响因子: --
作者:
McMichael AJ;Gotch FM;Rothbard J
通讯作者: Rothbard J
DOI: 10.1084/jem.165.2.459
发表时间: 1987-02-01
影响因子: 15.3
作者:
WATARI, E;DIETZSCHOLD, B;HEBERKATZ, E
通讯作者: HEBERKATZ, E
DOI: 10.1084/jem.163.4.903
发表时间: 1986-04-01
期刊: The Journal of experimental medicine
影响因子: --
作者:
Morrison LA;Lukacher AE;Braciale VL;Fan DP;Braciale TJ
通讯作者: Braciale TJ