Next Article in Journal
A Transcriptomic Approach to Understanding the Combined Impacts of Supra-Optimal Temperatures and CO2 Revealed Different Responses in the Polyploid Coffea arabica and Its Diploid Progenitor C. canephora
Previous Article in Journal
Hyaluronan Synthases’ Expression and Activity Are Induced by Fluid Shear Stress in Bone Marrow-Derived Mesenchymal Stem Cells
Article

Beta-1,3 Oligoglucans Specifically Bind to Immune Receptor CD28 and May Enhance T Cell Activation

1
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA
2
Molecular Graphics and Computation Facility, College of Chemistry, University of California, Berkeley, CA 94720, USA
3
Center for Bioinformatics, Simulation and Modeling (CBSM), Faculty of Engineering, Universidad de Talca, Talca 3460000, Chile
4
Euglena Co., Ltd., Tokyo 108-0014, Japan
5
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Paolo Gualtieri
Int. J. Mol. Sci. 2021, 22(6), 3124; https://doi.org/10.3390/ijms22063124
Received: 14 February 2021 / Revised: 4 March 2021 / Accepted: 10 March 2021 / Published: 18 March 2021
(This article belongs to the Special Issue Glucans, Paramylon and other Algae Bioactive Molecules)
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. View Full-Text
Keywords: beta glucans; oligoglucans; oligomers; CD28; CD3; T cell activation; immune stimulation; molecular dynamics simulation; free energy calculation beta glucans; oligoglucans; oligomers; CD28; CD3; T cell activation; immune stimulation; molecular dynamics simulation; free energy calculation
Show Figures

Figure 1

MDPI and ACS Style

Comer, J.; Bassette, M.; Burghart, R.; Loyd, M.; Ishiguro, S.; Azhagiya Singam, E.R.; Vergara-Jaque, A.; Nakashima, A.; Suzuki, K.; Geisbrecht, B.V.; Tamura, M. Beta-1,3 Oligoglucans Specifically Bind to Immune Receptor CD28 and May Enhance T Cell Activation. Int. J. Mol. Sci. 2021, 22, 3124. https://doi.org/10.3390/ijms22063124

AMA Style

Comer J, Bassette M, Burghart R, Loyd M, Ishiguro S, Azhagiya Singam ER, Vergara-Jaque A, Nakashima A, Suzuki K, Geisbrecht BV, Tamura M. Beta-1,3 Oligoglucans Specifically Bind to Immune Receptor CD28 and May Enhance T Cell Activation. International Journal of Molecular Sciences. 2021; 22(6):3124. https://doi.org/10.3390/ijms22063124

Chicago/Turabian Style

Comer, Jeffrey, Molly Bassette, Riley Burghart, Mayme Loyd, Susumu Ishiguro, Ettayapuram R. Azhagiya Singam, Ariela Vergara-Jaque, Ayaka Nakashima, Kengo Suzuki, Brian V. Geisbrecht, and Masaaki Tamura. 2021. "Beta-1,3 Oligoglucans Specifically Bind to Immune Receptor CD28 and May Enhance T Cell Activation" International Journal of Molecular Sciences 22, no. 6: 3124. https://doi.org/10.3390/ijms22063124

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop