期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 217, 期 10, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20200206
关键词
-
资金
- European Research Council [323183, 670955]
- Swiss National Science Foundation [149475]
- Commission of the European Communities, Seventh Framework Programme [HEALTH-2011-280873]
- Helmut Horten Stiftung
- European Research Council (ERC) [323183, 670955] Funding Source: European Research Council (ERC)
The importance of CD4(+) T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4(+) T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4(+) T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry-based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.
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