TY - JOUR
T1 - Glycoproteomic Analysis of MGL-Binding Proteins on Acute T-Cell Leukemia Cells
AU - Pirro, Martina
AU - Schoof, Esmee
AU - van Vliet, Sandra J.
AU - Rombouts, Yoann
AU - Stella, Alexandre
AU - de Ru, Arnoud
AU - Mohammed, Yassene
AU - Wuhrer, Manfred
AU - van Veelen, Peter A.
AU - Hensbergen, Paul J.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - C-type lectins are a diverse group of proteins involved in many human physiological and pathological processes. Most C-type lectins are glycan-binding proteins, some of which are pivotal for innate immune responses against pathogens. Other C-type lectins, such as the macrophage galactose-type lectin (MGL), have been shown to induce immunosuppressive responses upon the recognition of aberrant glycosylation on cancer cells. MGL is known to recognize terminal N-acetylgalactosamine (GalNAc), such as the Tn antigen, which is commonly found on malignant cells. Even though this glycan specificity of MGL is well described, there is a lack of understanding of the actual glycoproteins that bind MGL. We present a glycoproteomic workflow for the identification of MGL-binding proteins, which we applied to study MGL ligands on the human Jurkat leukemia cell line. In addition to the known MGL ligands and Tn antigen-carrying proteins CD43 and CD45 on these cells, we have identified a set of novel cell-surface ligands for MGL. Importantly, for several of these, O-glycosylation has hitherto not been described. Altogether, our data provide new insight into the identification and structure of novel MGL ligands that presumably act as modulatory molecules in cancer immune responses.
AB - C-type lectins are a diverse group of proteins involved in many human physiological and pathological processes. Most C-type lectins are glycan-binding proteins, some of which are pivotal for innate immune responses against pathogens. Other C-type lectins, such as the macrophage galactose-type lectin (MGL), have been shown to induce immunosuppressive responses upon the recognition of aberrant glycosylation on cancer cells. MGL is known to recognize terminal N-acetylgalactosamine (GalNAc), such as the Tn antigen, which is commonly found on malignant cells. Even though this glycan specificity of MGL is well described, there is a lack of understanding of the actual glycoproteins that bind MGL. We present a glycoproteomic workflow for the identification of MGL-binding proteins, which we applied to study MGL ligands on the human Jurkat leukemia cell line. In addition to the known MGL ligands and Tn antigen-carrying proteins CD43 and CD45 on these cells, we have identified a set of novel cell-surface ligands for MGL. Importantly, for several of these, O-glycosylation has hitherto not been described. Altogether, our data provide new insight into the identification and structure of novel MGL ligands that presumably act as modulatory molecules in cancer immune responses.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062370753&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30582698
U2 - https://doi.org/10.1021/acs.jproteome.8b00796
DO - https://doi.org/10.1021/acs.jproteome.8b00796
M3 - Article
C2 - 30582698
SN - 1535-3893
VL - 18
SP - 1125
EP - 1132
JO - Journal of proteome research
JF - Journal of proteome research
IS - 3
ER -