Mutation of the ER retention receptor KDELR1 leads to cell-intrinsic lymphopenia and a failure to control chronic viral infection

Chaperones in the endoplasmic reticulum (ER) are essential for protein folding and for the maintenance of an efficient secretory pathway. These chaperones can also accompany their substrates during transit from the ER to the Golgi. The prototypical mammalian KDEL receptor (KDELR1) functions by returning chaperones and other proteins to the ER. We show that a recessive missense mutation of Kdelr1 in mice is associated with low numbers of lymphocytes in the blood (lymphopenia), reduced expression of the T-cell receptor, and compromised antiviral immunity.