Cd4+ T Cells from Lupus-Prone Mice Are Hyperresponsive to T Cell Receptor Engagement with Low and High Affinity Peptide Antigens

Author:

Vratsanos George S.1,Jung Sungsoo1,Park Yeong-Min1,Craft Joe1

Affiliation:

1. Section of Rheumatology, Department of Medicine, and the Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520

Abstract

Polyclonal CD4+ T cell activation is characteristic of spontaneous lupus. As a potential explanation for this phenotype, we hypothesized that T cells from lupus-prone mice are intrinsically hyperresponsive to stimulation with antigen, particularly to those peptide ligands having a low affinity for the T cell receptor (TCR). To test this hypothesis, we backcrossed the α and β chain genes of the AND TCR specific for amino acids 88–104 of pigeon cytochrome C (PCC) to the Fas-intact MRL/Mp+Fas-lpr and to the H-2k–matched control backgrounds B10.BR and CBA/CaJ (MRL.AND, B10.AND, and CBA.AND, respectively), and assessed naive CD4+ TCR transgenic T cell activation in vitro after its encounter with cognate antigen and lower affinity altered peptide ligands (APLs). MRL.AND T cells, compared with control B10.AND and CBA.AND cells, proliferated more when stimulated with agonist antigen. More strikingly, MRL.AND T cells proliferated significantly more and produced more interleukin 2 when stimulated with the APLs of PCC 88–104, having lower affinity for the transgenic TCR. These results imply that one of the forces driving polyclonal activation of α/β T cells in lupus is an intrinsically heightened response to peptide antigen, particularly those with low affinity for the TCR, independent of the nature of the antigen-presenting cell and degree of costimulation.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Reference40 articles.

1. Treatment of murine lupus with monoclonal anti-T cell antibody;Wofsy;J. Immunol.,1985

2. Murine lupus in the absence of αβ T cells;Peng;J. Immunol,1996

3. Evidence for polyclonal T cell activation in murine models of systemic lupus erythematosus;Rozzo;J. Immunol,1994

4. Central T cell tolerance in lupus-prone miceinfluence of autoimmune background and the lpr mutation;Fatenejad;J. Immunol,1998

5. Altered peptide ligand-induced partial T cell activationmolecular mechanisms and role in T cell biology;Sloan-Lancaster;Annu. Rev. Immunol.,1996

Cited by 93 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3