ArticleThe Journal of experimental medicine2001
Negative selection during the peripheral immune response to antigen.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 164 citations in OpenAlex.
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- Antigen-specific immunotherapy with apitopes suppresses generation of FVIII inhibitor antibodies in HLA-transgenic mice.Blood advances · 2022Article
- Influence of DM-sensitivity on immunogenicity of MHC class II restricted antigens.Journal for immunotherapy of cancer · 2021Article
- Manipulating antigen presentation for antigen-specific immunotherapy of autoimmune diseases.Current opinion in immunology · 2021Review
- Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics.Frontiers in immunology · 2021Review
- Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection.Nature immunology · 2020Article
- PD-1 expression is upregulated on adapted T cells in experimental autoimmune encephalomyelitis but is not required to maintain a hyporesponsive state.European journal of immunology · 2019Article
- NFM Cross-Reactivity to MOG Does Not Expand a Critical Threshold Level of High-Affinity T Cells Necessary for Onset of Demyelinating Disease.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Molecular mimicry and autoimmune thyroid disease.Reviews in endocrine & metabolic disorders · 2016Review
- Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response.Nature communications · 2016Article
- Narrowing the Gap: Preserving Repertoire Diversity Despite Clonal Selection during the CD4 T Cell Response.Frontiers in immunology · 2015Review
- Antigen signal strength during priming determines effector CD4 T cell function and antigen sensitivity during influenza virus challenge.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- HLA-DM constrains epitope selection in the human CD4 T cell response to vaccinia virus by favoring the presentation of peptides with longer HLA-DM-mediated half-lives.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- CD8 T cell autoreactivity to preproinsulin epitopes with very low human leucocyte antigen class I binding affinity.Clinical and experimental immunology · 2012Article
- Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4⁺ T-cell repertoire selection.Nature communications · 2012Article
- Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Functional avidity: a measure to predict the efficacy of effector T cells?Clinical & developmental immunology · 2012Review
- Low 2-dimensional CD4 T cell receptor affinity for myelin sets in motion delayed response kinetics.PloS one · 2012Article
- Altered differentiation, diminished pathogenicity, and regulatory activity of myelin-specific T cells expressing an enhanced affinity TCR.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Thymic selection depends on positive and negative selective mechanisms based on the avidity of T cell interaction with antigen-major histocompatibility complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence for an avidity-based model of peripheral T cell clonal expansion in response to antigenic challenge. We have used the encephalitogenic, H-2 A(u)-restricted, acetylated NH(2)-terminal nonameric peptide (Ac1-9) epitope from myelin basic protein as our model antigen. Peptide analogues were generated that varied in antigenic strength (as assessed by in vitro assay) based on differences in their binding affinity for A(u). In vivo, these analogues elicited distinct repertoires of T cells that displayed marked differences in antigen sensitivity. Immunization with the weakest (wild-type) antigen expanded the high affinity T cells required to induce encephalomyelitis. In contrast, immunization with strongly antigenic analogues led to the elimination of T cells bearing high affinity T cell receptors by apoptosis, thereby preventing disease development. Moreover, the T cell repertoire was consistently tuned to respond to the immunizing antigen with the same activation threshold. This tuning mechanism provides a peripheral control against the expansion of autoreactive T cells and has implications for immunotherapy and vaccine design.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.