Structural clues for unraveling the first stage of lipid-antigen presentation in immune responses to allergies

The complex response of the human immune system to the presence of hazardous molecules is triggered through their recognition by T-cell receptors facilitated by antigen-presenting proteins. We have found structural clues of the lipid-presenting CD1d protein that may help elucidate the mechanism of initial lipid-loading stages of the whole process.


The immune responses to the presence of possibly hazardous substances such as those causing allergies to plant food are an extremely complex process. The initial stage of this process is the loading of a molecule (the antigen) onto a protein responsible for presenting it to T-cell receptors. While this loading is well characterized for peptide antigens, it is poorly understood for lipid antigens. CD1d is a key protein in charge of presenting lipid antigens and known to play a role in the onset of allergic symptoms. Besides, increasing evidence suggest that many food allergies may be triggered by lipid cargo carried by allergen proteins. In this paper, which is the first part of our structural study on CD1d, we have found physicochemical and structural features of this protein that may help elucidate how this lipid loading occurs. Our results from computational modelling, molecular dynamics simulations and calculations of electrostatic potentials and electric fields, reveal that those features are pH-dependent and reflect into a high plasticity of the entry to an internal hydrophobic cavity of CD1d.


Original Paper:

Cuevas-Zuviría, B., Mínguez-Toral, M., Díaz-Perales, A., Garrido-Arandia, M., Pacios, L.F. 2020. Dynamic plasticity of the lipid antigen-binding site of CD1d is crucially favoured by acidic pH and helper proteins. Scientific Reports 10, 5714. DOI: 10.1038/s41598-020-62833-y