MGL receptor and immunity: when the ligand can make the difference

C-type lectin receptors (CLRs) on antigen-presenting cells (APCs) facilitate uptake of carbohydrate antigens for antigenpresentation, modulating the immune response in infection, homeostasis, autoimmunity, allergy, and cancer. In this review, wefocus on the role of the macrophage galactose type C-type lectin (MGL) in the immune response against self-antigens, pathogens,and tumor associated antigens (TAA). MGL is a CLR exclusively expressed by dendritic cells (DCs) and activated macrophages(MØs), able to recognize terminal GalNAc residues, including the sialylated and nonsialylated Tn antigens.We discuss the effects onDC function induced throughout the engagement ofMGL, highlighting the importance of the antigen structure in the modulationof immune response. Indeed modifying Tn-density, the length, and steric structure of the Tn-antigens can result in generatingimmunogens that can efficiently bind to MGL, strongly activate DCs, mimic the effects of a danger signal, and achieve an efficientpresentation in HLA classes I and II compartments.