期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 37, 期 3, 页码 602-612出版社
WILEY
DOI: 10.1002/eji.200636787
关键词
autoimmunity; multispecific response; TCR
类别
资金
- NIAID NIH HHS [P01AI39671] Funding Source: Medline
- NINDS NIH HHS [NS24247] Funding Source: Medline
The paradox of autoreactivity to self-peptides in physiological as opposed to pathological immune responses is not well understood. Here, we directly examined the human T cell response to endogenous self-peptides in a series of healthy subjects. CFSE-labeled T cells were stimulated with unmanipulated antigen-presenting cells containing endogenous self-antigen, and the resulting CD4(+) populations entering into cell cycle (CFSElow) or non-proliferating CD4(+) cells (CFSEhigh) were single-cell sorted, cloned and screened against a panel of self-antigens and microbial recall antigens to interrogate their antigen reactivity. The percentage of CD4(+) T cells entering cell cycle in response to self-peptide/MHC was calculated to be 0.04%, and entry into cell cycle was dependent upon CD28 costimulation. Clones derived from CFSElow T cells exhibited significantly greater cross-reactivity to multiple antigens than CFSEhigh clones or other CD4(+) clones generated after microbial antigen stimulation. Sequencing the TCRP chains indicated that CFSElow clones were indeed clonal. These data demonstrate that T cell clones generated on stimulation by endogenous self-peptides exhibit a high degree of multispecificity, and we speculate that their multispecificity is based upon recognition of shared-backbone MHC determinants.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据