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鸡卵清溶菌酶内的一个有限区域是多种T细胞克隆的聚焦点。

A limited region within hen egg-white lysozyme serves as the focus for a diversity of T cell clones.

作者信息

Manca F, Clarke J A, Miller A, Sercarz E E, Shastri N

出版信息

J Immunol. 1984 Oct;133(4):2075-8.

PMID:6206149
Abstract

The C57BL/6 (H-2b) mouse is a nonresponder to hen egg-white lysozyme (HEL) injected i.p., owing to a T suppressor cell-inducing determinant at the amino-terminal region. After immunization with a 93-amino acid fragment (a.a. 13-105) of HEL lacking this determinant, all clones from two independently derived C57BL/6 T cell lines were found to be specific for epitopes within a subregion of peptide 74-96. Three specificity patterns for the clones could be defined on the basis of cross-reactivities with only two other species variant lysozymes. Reactivities of all three specificity groups was consistent with the serine to threonine substitution at position 91, although reactivity of one of the groups could be affected by substitutions at position 84. The results confirm at the clonal level that even for distantly related antigens, only limited regions are recognized by T cells. They are consistent with the notion that specific sites on the antigen capable of interaction with Ia molecules lead to dominance of certain regions for T cell reactivity. Moreover, the diversity in specificity among clones suggests that the limiting feature of T cell responsiveness is not a lack of available T cells in the repertoire directed against a single antigenic site.

摘要

C57BL/6(H-2b)小鼠对腹腔注射的鸡蛋清溶菌酶(HEL)无反应,这是由于其氨基末端区域存在一个诱导T抑制细胞的决定簇。在用缺乏该决定簇的HEL的93个氨基酸片段(第13 - 105位氨基酸)进行免疫后,发现来自两个独立衍生的C57BL/6 T细胞系的所有克隆对肽段74 - 96亚区域内的表位具有特异性。根据与仅另外两种物种变体溶菌酶的交叉反应性,可以确定克隆的三种特异性模式。所有三个特异性组的反应性与第91位丝氨酸到苏氨酸的取代一致,尽管其中一组的反应性可能受第84位取代的影响。结果在克隆水平上证实,即使对于远缘相关抗原,T细胞也仅识别有限的区域。它们与以下观点一致,即抗原上能够与Ia分子相互作用的特定位点导致某些区域在T细胞反应性方面占主导地位。此外,克隆间特异性的多样性表明,T细胞反应性的限制特征不是针对单个抗原位点的库中缺乏可用的T细胞。

相似文献

1
A limited region within hen egg-white lysozyme serves as the focus for a diversity of T cell clones.鸡卵清溶菌酶内的一个有限区域是多种T细胞克隆的聚焦点。
J Immunol. 1984 Oct;133(4):2075-8.
2
Constraints in antigen processing result in unresponsiveness to a T cell epitope of hen egg lysozyme in C57BL/6 mice.抗原加工过程中的限制导致C57BL/6小鼠对鸡蛋溶菌酶的T细胞表位无反应性。
Eur J Immunol. 1992 Mar;22(3):775-82. doi: 10.1002/eji.1830220322.
3
Amino acid residues distinct from the determinant region can profoundly affect activation of T cell clones by related antigens.与决定簇区域不同的氨基酸残基可深刻影响相关抗原对T细胞克隆的激活。
J Immunol. 1986 Jan;136(2):371-6.
4
Immunological focusing by th mouse major histocompatibility complex: mouse strains confronted with distantly related lysozymes confine their attention to very few epitopes.小鼠主要组织相容性复合体的免疫聚焦:面对远缘相关溶菌酶的小鼠品系将注意力集中在极少数表位上。
Eur J Immunol. 1982 Jul;12(7):535-40. doi: 10.1002/eji.1830120702.
5
The expressed T cell repertoire is hierarchical: the precise focus of lysozyme-specific T cell clones is dependent upon the structure of the immunogen.表达的T细胞库具有层次结构:溶菌酶特异性T细胞克隆的精确靶向取决于免疫原的结构。
J Mol Cell Immunol. 1984;1(6):369-79.
6
Epitope specificity of the T cell proliferative response to lysozyme: proliferative T cells react predominantly to different determinants from those recognized by B cells.T细胞对溶菌酶增殖反应的表位特异性:增殖性T细胞主要对与B细胞所识别的不同决定簇发生反应。
Eur J Immunol. 1980 Jul;10(7):509-15. doi: 10.1002/eji.1830100705.
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Analysis of T cell reactivities to phosphorylcholine-conjugated hen egg lysozyme in C57BL/6 mice: hapten-conjugate specificity reflects an altered expression of a major carrier epitope.C57BL/6小鼠中T细胞对磷酸胆碱偶联的鸡卵溶菌酶的反应性分析:半抗原偶联物特异性反映了主要载体表位表达的改变。
Eur J Immunol. 1991 May;21(5):1303-10. doi: 10.1002/eji.1830210531.
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Antigen presentation by dendritic cells focuses T cell responses against immunodominant peptides: studies in the hen egg-white lysozyme (HEL) model.树突状细胞的抗原呈递聚焦于针对免疫显性肽的T细胞反应:在鸡卵清溶菌酶(HEL)模型中的研究。
J Immunol. 1998 Feb 15;160(4):1555-64.
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The self-directed T cell repertoire against mouse lysozyme reflects the influence of the hierarchy of its own determinants and can be engaged by a foreign lysozyme.针对小鼠溶菌酶的自主T细胞库反映了其自身决定簇层次结构的影响,并且可被外源溶菌酶激活。
J Immunol. 1999 Oct 15;163(8):4232-7.
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Antigen-specific T helper clones in a nonresponder strain require augmentation for expression of helper activity. Evidence for a possible antigen presentation defect in B cells.无反应性品系中的抗原特异性辅助性T细胞克隆需要增强才能表达辅助活性。B细胞中可能存在抗原呈递缺陷的证据。
J Immunol. 1984 Sep;133(3):1215-21.

引用本文的文献

1
Increasing the foreignness of an antigen, by coupling a second and foreign antigen to it, increases the T helper type 2 component of the immune response to the first antigen.通过将第二种外来抗原与第一种抗原偶联来增加抗原的异源性,会增强针对第一种抗原的免疫反应中2型辅助性T细胞成分。
Immunology. 2005 May;115(1):34-41. doi: 10.1111/j.1365-2567.2005.02128.x.
2
T cell clones specific for an amphipathic alpha-helical region of sperm whale myoglobin show differing fine specificities for synthetic peptides. A multiview/single structure interpretation of immunodominance.针对抹香鲸肌红蛋白两亲性α-螺旋区域的T细胞克隆对合成肽表现出不同的精细特异性。免疫显性的多视角/单一结构解读。
J Exp Med. 1986 Nov 1;164(5):1779-84. doi: 10.1084/jem.164.5.1779.
3
Structural basis of antigen recognition by T lymphocytes. Implications for vaccines.
T淋巴细胞对抗原识别的结构基础。对疫苗的启示。
J Clin Invest. 1988 Dec;82(6):1811-7. doi: 10.1172/JCI113796.
4
Helper T-cell clones that recognize autologous insulin are stimulated in nonresponder mice by pork insulin.在无反应小鼠中,识别自身胰岛素的辅助性T细胞克隆会被猪胰岛素刺激。
Proc Natl Acad Sci U S A. 1988 Apr;85(8):2723-7. doi: 10.1073/pnas.85.8.2723.
5
Class II-restricted T-cell clones to a synthetic peptide of influenza virus hemagglutinin differ in their fine specificities and in the ability to respond to virus.针对流感病毒血凝素合成肽的II类限制性T细胞克隆,在其精细特异性和对病毒的反应能力方面存在差异。
J Virol. 1989 Jul;63(7):3087-94. doi: 10.1128/JVI.63.7.3087-3094.1989.
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A sequence pattern common to T cell epitopes.一种T细胞表位共有的序列模式。
EMBO J. 1988 Jan;7(1):93-100. doi: 10.1002/j.1460-2075.1988.tb02787.x.
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Limiting dilution comparison of the repertoires of high and low responder MHC-restricted T cells.高反应性和低反应性MHC限制性T细胞库的有限稀释比较。
J Exp Med. 1988 Mar 1;167(3):1100-13. doi: 10.1084/jem.167.3.1100.
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Helper T-cell antigenic site identification in the acquired immunodeficiency syndrome virus gp120 envelope protein and induction of immunity in mice to the native protein using a 16-residue synthetic peptide.在获得性免疫缺陷综合征病毒gp120包膜蛋白中鉴定辅助性T细胞抗原位点,并使用一个16个残基的合成肽诱导小鼠对天然蛋白产生免疫。
Proc Natl Acad Sci U S A. 1987 Jun;84(12):4249-53. doi: 10.1073/pnas.84.12.4249.
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Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes.利用流感病毒核蛋白的合成肽来确定由I类限制性细胞毒性T淋巴细胞识别的表位。
J Exp Med. 1987 Jun 1;165(6):1508-23. doi: 10.1084/jem.165.6.1508.
10
Ia molecule-associated selectivity in T cell recognition of a 23-amino-acid peptide of lysozyme.Ia分子在T细胞识别溶菌酶23个氨基酸肽段中的相关选择性。
J Exp Med. 1986 Sep 1;164(3):882-96. doi: 10.1084/jem.164.3.882.