Beta-1,3 Oligoglucans Specifically Bind to Immune Receptor CD28 and May Enhance T Cell Activation
| Autor: | Brian V. Geisbrecht, Susumu Ishiguro, Ariela Vergara-Jaque, Molly Bassette, Jeffrey Comer, Ettayapuram Ramaprasad Azhagiya Singam, Ayaka Nakashima, Kengo Suzuki, Masaaki Tamura, Riley Burghart, Mayme Loyd |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular 0301 basic medicine beta-Glucans T-Lymphocytes Immune receptor Lymphocyte Activation 01 natural sciences lcsh:Chemistry Jurkat Cells free energy calculation beta glucans Receptors Immunologic Receptor lcsh:QH301-705.5 Spectroscopy 010304 chemical physics T cell activation Chemistry CD28 General Medicine Computer Science Applications Cell biology molecular dynamics simulation medicine.anatomical_structure Cytokines Thermodynamics Protein Binding immune stimulation T cell T-Cell Receptor Activation Article Catalysis Inorganic Chemistry 03 medical and health sciences CD28 Antigens 0103 physical sciences medicine Humans oligomers Physical and Theoretical Chemistry Binding site Molecular Biology CD86 oligoglucans Organic Chemistry CD3 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 CD80 |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 6 International Journal of Molecular Sciences, Vol 22, Iss 3124, p 3124 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22063124 |
| Popis: | Beta glucans are known to have immunomodulatory effects that mediated by a variety of mechanisms. In this article, we describe experiments and simulations suggesting that beta-1,3 glucans may promote activation of T cells by a previously unknown mechanism. First, we find that treatment of a T lymphoblast cell line with beta-1,3 oligoglucan significantly increases mRNA levels of T cell activation-associated cytokines, especially in the presence of the agonistic anti-CD3 antibody. This immunostimulatory activity was observed in the absence of dectin-1, a known receptor for beta-1,3 glucans. To clarify the molecular mechanism underlying this activity, we performed a series of molecular dynamics simulations and free-energy calculations to explore the interaction of beta-1,3 oligoglucans with potential immune receptors. While the simulations reveal little association between beta-1,3 oligoglucan and the immune receptor CD3, we find that beta-1,3 oligoglucans bind to CD28 near the region identified as the binding site for its natural ligands CD80 and CD86. Using a rigorous absolute binding free-energy technique, we calculate a dissociation constant in the low millimolar range for binding of 8-mer beta-1,3 oligoglucan to this site on CD28. The simulations show this binding to be specific, as no such association is computed for alpha-1,4 oligoglucan. This study suggests that beta-1,3 glucans bind to CD28 and may stimulate T cell activation collaboratively with T cell receptor activation, thereby stimulating immune function. |
| Databáze: | OpenAIRE |
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