ArticleJournal of immunology (Baltimore, Md. : 1950)2018
Peptide-MHC Class I Tetramers Can Fail To Detect Relevant Functional T Cell Clonotypes and Underestimate Antigen-Reactive T Cell Populations.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 84 citations in OpenAlex.
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- Defining Functional T Cell Receptor Repertoires With Nanovial-Based Screening.Immunological reviews · 2026Review
- HLA-E-restricted T cells primed by a modified HLA-B*57:01-restricted HIV-1 peptide suppress HIV-1 replication.JCI insight · 2026Article
- Unbiased avidity-based isolation of antigen-specific T cells.Journal for immunotherapy of cancer · 2026Article
- An affinity reagent-conjugated biotin ligase for amplified cell surface labelling in vitro and in vivo.Scientific reports · 2026Article
- Newly identified oncolytic VSV-GP-specific CD8Molecular therapy. Oncology · 2025Article
- PredIG: an interpretable predictor of T-cell epitope immunogenicity.Genome medicine · 2025Article
- ATLAS-seq: a microfluidic single-cell TCR screen for antigen-reactive TCRs.Nature communications · 2025Article
- Comprehensive self-antigen screening to assess cross-reactivity in promiscuous T-cell receptors.Frontiers in immunology · 2025Article
- HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.The Journal of clinical investigation · 2024Article
- The Altered Neonatal CD8Viruses · 2024Article
- CD3 aptamers promote expansion and persistence of tumor-reactive T cells for adoptive T cell therapy in cancer.Molecular therapy. Nucleic acids · 2024Article
- Low-affinity CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
- De novo identification of CD4Nature methods · 2024Article
- Neo-Antigen-Reactive T Cells Immunotherapy for Colorectal Cancer: A More Personalized Cancer Therapy Approach.Global challenges (Hoboken, NJ) · 2023Review
- Barcoding intracellular reverse transcription enables high-throughput phenotype-coupled T cell receptor analyses.Cell reports methods · 2023Article
- What's the Catch? The Significance of Catch Bonds in T Cell Activation.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Dissecting the Protective Effect of CD8Biology · 2023Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
Peptide-MHC (pMHC) multimers, usually used as streptavidin-based tetramers, have transformed the study of Ag-specific T cells by allowing direct detection, phenotyping, and enumeration within polyclonal T cell populations. These reagents are now a standard part of the immunology toolkit and have been used in many thousands of published studies. Unfortunately, the TCR-affinity threshold required for staining with standard pMHC multimer protocols is higher than that required for efficient T cell activation. This discrepancy makes it possible for pMHC multimer staining to miss fully functional T cells, especially where low-affinity TCRs predominate, such as in MHC class II-restricted responses or those directed against self-antigens. Several recent, somewhat alarming, reports indicate that pMHC staining might fail to detect the majority of functional T cells and have prompted suggestions that T cell immunology has become biased toward the type of cells amenable to detection with multimeric pMHC. We use several viral- and tumor-specific pMHC reagents to compare populations of human T cells stained by standard pMHC protocols and optimized protocols that we have developed. Our results confirm that optimized protocols recover greater populations of T cells that include fully functional T cell clonotypes that cannot be stained by regular pMHC-staining protocols. These results highlight the importance of using optimized procedures that include the use of protein kinase inhibitor and Ab cross-linking during staining to maximize the recovery of Ag-specific T cells and serve to further highlight that many previous quantifications of T cell responses with pMHC reagents are likely to have considerably underestimated the size of the relevant populations.
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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.