Generally, C-type lectins bind carbohydrate moieties usually in the presence of Ca2+ and have diverse functions, such as
cell adhesion,
cell-cell signalling,
glycoprotein turnover, and roles in
inflammation and immune response. CLEC10A is a
type II transmembrane protein (passing one time through the membrane and oriented with the
N terminus inward) that induces
endocytosis after
ligand binding. To release the ligand in the
endosome, participating Ca2+ ions have to be unbound first. This leads to a significant increase in cytoplasmic Ca2+ concentration. This includes the
Tn antigen (GalNAc O-bound to serine or threonine) which is prominently expressed on
carcinomas, where it can also be
sialylated. These
tumor-associated antigens (Neu5Acα2,6-Tn, and NeuGcα2,6-Tn) are also bound. CLEC10A has also been shown to bind GalNAc in the teichoic acid of the Staphylococcus aureus cell wall and the surface of parasites. CLEC10A is expressed by dendritic cells that differentiate from
monocytes recruited to inflammatory environments.
CD45 contains a Tn antigen in
exon B. CD45 has 3 important exons (4,5,6), that are designated A,B,C.
Isoforms of CD45 are labeled depending on the presence of these exons. CLEC10A can for example bind CD45RB or CD45R, which is shorthand for CD45RABC. Binding causes attenuation of
T cell activity,
apoptosis, and
immunosuppression. However, active T cells express shorter isoforms of CD45 (CD45RO, CD45RA) that lack exon B. and worsen survival. In animal models, deficiency of the orthologue to CLEC10A, Mgl1 is associated with worse outcomes in infection and excessive inflammation. == References ==