This illustration by Erica Tandori explores how smoke components in cigarette & e-cigarette smoke obscures critical molecules like smoke-binding ligands & MR1 complexes, disrupting T-cell responses

This discovery is a key step in understanding how #Cigarette smoke disrupts the immune system and contribute to deadly lung disease.

Interestingly, mice lacking MAIT cells (MR1 deficiency) demonstrated partially protection against the development of cigarette-induced COPD.
Thus, #cigarette smoking can impair #MAIT functions, and potentially contribute to infection susceptibility and disease exacerbations.

Then, we discovered via mice studies that Chronic CS exposure altered MAIT cell phenotype and function in vivo, which increases susceptibility to influenza A virus infection and exacerbates COPD.

Protein crystallography was next used to ascertain the molecular basis of MR1 binding of CS components, and we found that these compounds bound the MR1 ligand binding pocket via forming a covalent interaction with Lys-43, a key residue of MR1.

These adverse effects of smoking on immunity not only occur in active smokers, but also in those exposed to smoke passively in contaminated environments and may persist for decades after exposure has ended. These CS ligands found to moderately impair MAIT activity ex vivo.

We the identified components of CS that MR1 detect using in silico and cellular assays. This includes nicotinaldehyde, thirdhand CS component, which give the smell of the smoke on clothes, cars, inside the house and including flavourings in cigarettes, e-cigarettes.

First, we discovered that CS extract changes
MAIT cell activation in vitro and increases MR1 surface expression. We suspected that some of the more than 20,000 chemicals present in cigarette smoke that smokers inhale might bind to MR1 and influence the T cells in the lungs