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一种在人类免疫缺陷病毒1逆转录酶中被小鼠和人类细胞毒性T淋巴细胞识别的表位。

An epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes.

作者信息

Hosmalin A, Clerici M, Houghten R, Pendleton C D, Flexner C, Lucey D R, Moss B, Germain R N, Shearer G M, Berzofsky J A

机构信息

Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

出版信息

Proc Natl Acad Sci U S A. 1990 Mar;87(6):2344-8. doi: 10.1073/pnas.87.6.2344.

Abstract

T-cell-mediated cytotoxicity may play an important role in control of infection by the human immunodeficiency virus (HIV). In this study, we have identified and characterized a relatively conserved epitope in the HIV-1 reverse transcriptase recognized by murine and human cytotoxic T cells. This epitope was identified using a murine antigen-specific CD8+ class I major histocompatibility complex-restricted cytotoxic T-cell (CTL) line, a transfected fibroblast cell line expressing the HIV-1 pol gene, recombinant vaccinia viruses containing different truncated versions of the pol gene, and overlapping synthetic peptides. The optimal antigenic site was identified as residues 203-219 by synthesizing extended or truncated peptide analogs of the antigenic fragment. The optimal peptide was then tested for sensitization of autologous Epstein-Barr virus-transformed B-cell targets for killing by fresh human peripheral blood mononuclear cells. It was recognized by CTLs from several HIV-seropositive patients but not from any seronegative donor. Therefore, this peptide is a good candidate for inclusion in an AIDS vaccine. This study demonstrates that the same CTL epitope can be seen by murine and human CD8+ CTLs, as previously demonstrated for epitopes recognized by CD4+ helper T cells, and suggests the utility of screening for immunodominant CTL epitopes in mice prior to carrying out studies in humans.

摘要

T细胞介导的细胞毒性可能在控制人类免疫缺陷病毒(HIV)感染中发挥重要作用。在本研究中,我们鉴定并表征了HIV-1逆转录酶中一个相对保守的表位,该表位可被小鼠和人类细胞毒性T细胞识别。使用小鼠抗原特异性CD8⁺ I类主要组织相容性复合体限制的细胞毒性T细胞(CTL)系、表达HIV-1 pol基因的转染成纤维细胞系、含有不同截短版本pol基因的重组痘苗病毒以及重叠合成肽来鉴定该表位。通过合成抗原片段的延伸或截短肽类似物,将最佳抗原位点鉴定为203 - 219位氨基酸残基。然后测试最佳肽对自体爱泼斯坦-巴尔病毒转化的B细胞靶标的致敏作用,以被新鲜的人类外周血单个核细胞杀伤。它被来自几名HIV血清阳性患者的CTL识别,但未被任何血清阴性供体的CTL识别。因此,该肽是纳入艾滋病疫苗的良好候选物。本研究表明,小鼠和人类CD8⁺ CTL可以识别相同的CTL表位,正如之前针对CD4⁺辅助性T细胞识别的表位所证明的那样,并提示在对人类进行研究之前,在小鼠中筛选免疫显性CTL表位的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c68/53683/21303e363418/pnas01031-0309-a.jpg

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