ArticleProceedings of the National Academy of Sciences of the United States of America2011
Alloreactivity is limited by the endogenous peptide repertoire.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
25 citing papers in PubMed, 40 citations in OpenAlex.
- Guiding pluripotent stem cell therapies past the immune system.Stem cells translational medicine · 2026Review
- Unraveling CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- Mechanisms of allorecognition and xenorecognition in transplantation.Clinical transplantation and research · 2024Review
- Allorecognition Unveiled: Integrating Recent Breakthroughs Into the Current Paradigm.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Antibody-drug conjugates plus Janus kinase inhibitors enable MHC-mismatched allogeneic hematopoietic stem cell transplantation.The Journal of clinical investigation · 2021Article
- The role of self-peptides in direct T cell allorecognition.The Journal of clinical investigation · 2021Article
- Adapting T Cell Receptor Ligand Discrimination CapabilityFrontiers in immunology · 2021Review
- Quantifying size and diversity of the human T cell alloresponse.JCI insight · 2018Article
- Alloimmune T cells in transplantation.The Journal of clinical investigation · 2017Review
- Class II major histocompatibility complex mutant mice to study the germ-line bias of T-cell antigen receptors.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Low-Affinity Memory CD8+ T Cells Mediate Robust Heterologous Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Self-pMHCII complexes are variably expressed in the thymus and periphery independent of mRNA expression but dependent on the activation state of the APCs.Molecular immunology · 2015Article
- Generation of human alloantigen-specific T cells from peripheral blood.Journal of visualized experiments : JoVE · 2014Article
- The ability to rearrange dual TCRs enhances positive selection, leading to increased Allo- and Autoreactive T cell repertoires.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Effect of CDR3 sequences and distal V gene residues in regulating TCR-MHC contacts and ligand specificity.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- A stepwise model of polyreactivity of the T cell antigen-receptor (TCR): its impact on the self-nonself discrimination and on related observations (receptor editing, anergy, dual receptor cells).Cellular and molecular life sciences : CMLS · 2014Review
- Article
- Candida-elicited murine Th17 cells express high Ctla-4 compared with Th1 cells and are resistant to costimulation blockade.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Dual receptor T cells mediate pathologic alloreactivity in patients with acute graft-versus-host disease.Science translational medicine · 2013Article
- Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity.Immunology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A significant portion of the naive T-cell repertoire is capable of responding to allogeneic MHC, violating the paradigm of self-MHC restriction. Recent studies have demonstrated convincing evidence for germ-line affinity of T-cell receptors (TCR) for MHC, providing explanation for recognition of MHC not encountered during thymic development. However, although germ-line affinity proposes all TCR have inherent affinity for MHC, most T cells are not alloreactive to a given MHC. We propose that specific recognition of endogenous presented peptides, rather than inability to interact with allogeneic MHC molecules, is the primary determinant of alloreactivity. Here, we demonstrate that alloreactive and nonalloreactive TCR differ specifically in the CDR3 sequences responsible primarily for the peptide specificity of T-cell recognition. Limitations on alloreactivity imposed by a requirement for recognition of presented peptides are directly demonstrated by expansion of the alloreactive T-cell repertoire through the addition of peptide mimotopes enabling response to two distinct allogeneic MHC by otherwise nonalloreactive T cells. Responses to peptide mimotopes were specific and depended on TCR interaction with MHC. These results demonstrate that recognition of presented endogenous peptides, and not the inability to interact with allogeneic MHC, is the primary limiter on alloreactivity. This observation reconciles the concept of an inherently MHC-reactive TCR repertoire with observed frequencies of T cells responding to allogeneic stimulation and underscores the fundamental nature of TCR recognition of ligands, where both MHC and presented peptides contribute critically to T-cell recognition.
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Registered trials
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.