CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery
Open accessAbstract
The activation of T lymphocytes (T cells) requires signaling through the T-cell receptor (TCR). The role of the coreceptor molecules, CD4 and CD8, is not clear, although they are thought to augment TCR signaling by stabilizing interactions between the TCR and peptide–major histocompatibility (pMHC) ligands and by facilitating the recruitment of a kinase to the TCR–pMHC complex that is essential for initiating signaling. Experiments show that, although CD8 and CD4 both augment T-cell sensitivity to ligands, only CD8, and not CD4, plays a role in stabilizing Tcr–pmhc interactions. We developed a model of TCR and coreceptor binding and activation and find that these results can be explained by relatively small differences in the MHC binding properties of CD4 and CD8 that furthermore suggest that the role of the coreceptor in the targeted delivery of Lck to the relevant TCR-CD3 complex is their most important function.
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T cell activation relies on the recognition of peptide antigens in the context of major histocompatibility complex (MHC) molecules.
“However, T cell activation relies on the recognition of peptide antigens in the context of major histocompatibility complex (MHC) molecules [7].”
From Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis (2023) · cites this paper as [7]
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“However, T cell activation relies on the recognition of peptide antigens in the context of major histocompatibility complex (MHC) molecules [7].”
BackgroundDa Rocha, S., Bigot, J., Onodi, F., Cosette, J., Corre, G., Poupiot, J., Fenard, D., Gjata, B., Galy, A., & Neildez-Nguyen, T. M. A. (2019) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2019.06.011 · Cited by 12 · see citing works
- Authors
- Artyomov, M. N., Lis, M., Devadas, S., Davis, M. M., & Chakraborty, A. K.
- Affiliations
- Broad Institute (US)
- MIT Computer Science and Artificial Intelligence Laboratory (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-09-13
- Volume
- 107
- Issue
- 39
- Pages
- 16916-16921
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2947881
- OpenAlex
- W2059422010
- Cited by
- 207
- References
- 22
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 14 · 2022: 19 · 2021: 15 · 2020: 19 · 2019: 18 · 2018: 15 · 2017: 8 · 2016: 7 · 2015: 9 · 2014: 15 · 2013: 15 · 2012: 16
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (5p01ai071195-05)
- National Institute of Allergy and Infectious Diseases (P01AI-071195, 1P01/AI071195/01)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- CD4, CD8, T cell receptor signaling, Lck kinase, MHC binding, TCR-pMHC interaction, TCR/CD3 complex, T cell activation, ligand sensitivity
- MeSH terms
- Animals, Antigen-Presenting Cells, Humans, Lymphocyte Activation, Major Histocompatibility Complex, Receptors, Antigen, T-Cell, T-Lymphocytes, CD4 Antigens, CD8 Antigens, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Protein Transport
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