Research ArticleADAPTIVE IMMUNITY

Absence of MHC class II on cDC1 dendritic cells triggers fatal autoimmunity to a cross-presented self-antigen

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Science Immunology  13 Mar 2020:
Vol. 5, Issue 45, eaba1896
DOI: 10.1126/sciimmunol.aba1896

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Cross-tolerization tale

Conventional type 1 dendritic cells (cDC1s) present exogenous antigen on MHCI to CD8+ T cells through the process of cross-presentation. Wohn et al. now show that MHCII on cDC1s is required for cross-tolerization of CD8+ T cells. They developed a mouse model in which Cre recombinase is expressed under control of the cDC1 marker XC chemokine receptor (XCR1) to generate mice that are specifically lacking MHCII on cDC1 cells. MHCII-deficient cDC1s could not cross-tolerize autoreactive CD8+ T cells but instead converted them into effector CD8+ T cells that caused a lethal autoimmune response. The ability of cDC1s to enforce cross-tolerization is not completely acquired during homeostatic maturation but requires MHCII-restricted interactions with regulatory T cells.

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