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. 2023 Oct 17;33(11):879–887. doi: 10.1093/glycob/cwad083

Tn antigen interactions of macrophage galactose-type lectin (MGL) in immune function and disease

Berna Tumoglu 1, Aidan Keelaghan 2, Fikri Y Avci 3,✉
PMCID: PMC10859631  PMID: 37847609

Abstract

Protein-carbohydrate interactions are essential in maintaining immune homeostasis and orchestrating inflammatory and regulatory immune processes. This review elucidates the immune interactions of macrophage galactose-type lectin (MGL, CD301) and Tn carbohydrate antigen. MGL is a C-type lectin receptor (CLR) primarily expressed by myeloid cells such as macrophages and immature dendritic cells. MGL recognizes terminal O-linked N-acetylgalactosamine (GalNAc) residue on the surface proteins, also known as Tn antigen (Tn). Tn is a truncated form of the elongated cell surface O-glycan. The hypoglycosylation leading to Tn may occur when the enzyme responsible for O-glycan elongation—T-synthase—or its associated chaperone—Cosmc—becomes functionally inhibited. As reviewed here, Tn expression is observed in many different neoplastic and non-neoplastic diseases, and the recognition of Tn by MGL plays an important role in regulating effector T cells, immune suppression, and the recognition of pathogens.

Keywords: carbohydrate antigen, Cosmc chaperone, immune regulation, macrophage galactose-type lectin (MGL), Tn antigen

Introduction

Complex glycans and glycoconjugates comprised of glycoproteins, proteoglycans, polysaccharides, and glycolipids decorate virtually all cell surfaces (Cummings and McEver 2009; Stanley et al. 2022). Glycans have fundamental roles such as intercellular signaling, antigen recognition, and membrane organization (Varki 2017; Cummings et al. 2022). However, pathogens can exploit these fundamental roles by displaying host glycans on their surfaces to evade immune recognition in a process known as molecular mimicry, which is also referred to as glycan gimmickry during parasite-host interactions (van Die and Cummings 2009; Varki 2017; Cummings et al. 2022). For example, many viral pathogens mask their surface proteins with host glycans to evade host immune responses (Varki 2017). Protein glycosylation primarily takes place in the form of O-glycosylation of serine or threonine residues or N-glycosylation of asparagine residues, requiring specific amino acid sequons to initiate glycosylation pathways. Tn antigen is the product of the first step in O-glycosylation of a serine or threonine residue (Ju et al. 2011). T-synthase performs an essential step in elongating the O-glycan by adding a galactose residue to Tn antigen. T-synthase dysfunction, which commonly occurs due to loss of function in its chaperone Cosmc, leads to the expression of Tn antigen (Tn) and sialylated Tn antigen (sTn) (Ju et al. 2011). The abnormal expression of Tn has been associated with numerous pathologies (Ju et al. 2011).

Lectins play key roles in immune cell trafficking, adhesion, and signaling during immune development, homeostasis, and activation (Zizzari et al. 2015; Varki 2017; Paschall et al. 2023). C-Type lectins are a family of calcium-dependent receptors that recognize glycans. These receptors play important roles in regulating immune pathways such as antigen presentation, pathogen recognition, and internalization (Tsuiji et al. 2002) and are primarily located on the surface of myeloid APCs (McGreal et al. 2005). C-type lectins belong to one of two subgroups depending on their carbohydrate specificity: type I transmembrane receptors (e.g. MR, DEC-205) and type II transmembrane receptors (e.g. Dectin-1, DC-SIGN, MGL, Langerin) (Zizzari et al. 2015). Here, we review the immune function of MGL as an important immune cell surface receptor, the complex interplay between Tn antigen and MGL, and its manifestations in immune function and homeostasis.

MGL

MGL (CD301), a type II transmembrane protein, is highly expressed by immature dendritic cells and macrophages (Zizzari et al. 2015) and binds terminal GalNAc residues on numerous glycans such as Tn, sTn, and LacdiNAc. The glycan binding is coordinated by a Gln-Pro-Asp sequence in the carbohydrate recognition domain (CRD) (van Vliet et al. 2008; Marcelo et al. 2019; Pirro et al. 2020). MGL has a high affinity for O-linked GalNAc residues, which are expressed on self (CD45) or altered self (MUC1) proteins (Zizzari et al. 2015). Additionally, these glycans can be expressed by pathogens such as filovirus, helminths, and bacteria (van Sorge et al. 2009). While MGL predominantly binds to Tn antigen, it is capable of binding to other ligands with a lower affinity, so long as they bear a terminal GalNAc residue. For example, recent studies have shown that MGL can bind LacdiNAc, an N-glycan component found on colorectal cancer cell lines (Pirro et al. 2020).

MGL is encoded by the CLEC10A gene, located on human chromosome 17p13 (van Vliet et al. 2008; Zizzari et al. 2015). In contrast to human MGL (hMGL); there are two murine orthologs, MGL-1(CD301a) and MGL-2(CD301b), each with distinct glycan specificity. MGL-2 is encoded by the Mgl2 gene located on chromosome 11B3 (van Vliet et al. 2008), and it is the functional homolog of hMGL due to its specificity for the same ligands (Singh et al. 2009; Gabba et al. 2021). MGL-2 binds Tn antigen while MGL-1 recognizes Lewis A and Lewis X expressed by cancer cells such as SW1116 colon cancer cells (Blanas et al. 2018; Paschall et al. 2023). The sequence similarity of the CRD of hMGL and MGL-2 versus hMGL and MGL-1 is 87% and 83.3%, respectively. The similarity between hMGL and MGL-2 is demonstrated in Fig. 1, in which a crystal structure of hMGL CRD with Tn bound (Gabba et al. 2021) is compared to an AlphaFold predicted structure of the MGL-2 CRD. The superposition of these two structures yielded an RMSD value of 0.449, a measure of distances between the alpha carbon structure of two proteins, indicating these structures are highly similar.

Fig. 1.

Fig. 1

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Structural models of human MGL and mouse MGL-2 carbohydrate recognition domain. A) Crystal structure of human MGL with Tn antigen bound (UniProt 6w12) and an AlphaFold predicted structure of mouse MGL-2 (UniProt Q8JZN1) rotated along the Y-axis. B) The solvent-accessible surface area of hMGL and MGL-2 with Tn antigen overlayed onto MGL-2. Adapted from Gabba et al. (2021). Created with BioRender.com.

MGL’s role in the immune regulatory pathways

The immune system utilizes a plethora of strategies, resources, and tools to defend the host against diseases, such as antigen-specific antibodies neutralizing or opsonizing pathogens or cytotoxic T cells killing the compromised cells (Murphy et al. 2011). This enormous power requires regulation of the effector arm of the immune system through regulatory immune mechanisms. For example, immunosuppressive cytokine-secreting, specialized subpopulations of innate or adaptive immune cells may regulate effector immune responses (Dasgupta et al. 2014; Kumamoto et al. 2016; Paschall et al. 2023). MGL is primarily displayed on the surface of myeloid cells associated with immunoregulatory function. MGL2+ murine dermal DCs (DDCs) have been identified as a subset of migratory DCs that reside in the dermis and submucosa of respiratory, reproductive, and gastrointestinal tracts (Denda-Nagai et al. 2010). DDCs endocytose antigens and present them via MHC II molecules (van Vliet et al. 2007; van Vliet et al. 2008). DDCs play a role in the differentiation of naïve helper T cells to Th2 cells (Denda-Nagai et al. 2010). Depletion of MGL2+ DCs in mouse models resulted in impaired Th2 differentiation, indicating MGL2 as a regulator for Th2 cell differentiation (Kumamoto et al. 2013). In addition to their roles in T cell differentiation, MGL2+ murine DCs express ligands for immune checkpoints (Gao et al. 2013; Kumamoto et al. 2013; Murakami et al. 2013). MGL2+ murine DCs were shown to express immune checkpoint receptors called Programmed cell death ligands (PDL1, PDL2) (Kumamoto et al. 2016; Kenkel et al. 2017). When MGL2-expressing cells were depleted, immune checkpoint blockade was no longer effective at expanding Tf helper cells or germinal B cells, nor at activating cytotoxic T cell responses (Kumamoto et al. 2016). In a murine model of pancreatic ductal adenocarcinoma, depletion of MGL2+ DCs resulted in the reduction of tumor progression, lowering the frequency of Tregs, and suppression of metastasis (Kenkel et al. 2017). In a colorectal cancer mouse model, BRAF mutation induced MGL2 ligand expression (Lenos et al. 2015). BRAF is a proto-oncogene identified in multiple tumor types, such as colorectal cancer, melanoma, glioma, breast cancer, and sarcoma (Owsley et al. 2021). BRAF is associated with an immunosuppressive microenvironment and poor prognosis (Lenos et al. 2015). The results of this study suggest a correlation between oncogenic transformation and immunosuppressive pathways (Lenos et al. 2015).

Tn antigen

T-synthase plays a key role in the O-glycosylation of proteins (Ju and Cummings 2010;Ju et al. 2014; Xiang et al. 2022). T-synthase transfers a galactose (Gal) residue from the donor UDP-Gal to synthesize the core 1 disaccharide Galβ1–3GalNAc⍺1-O-Ser/Thr, which is called Thomsen Friedenreich or T antigen (Fig. 2) (Reepmaker 1952; Uhlenbruck 1981). Tn antigen is a substrate for T-synthase and is the precursor of T-antigen (Xiang et al. 2022). Proper activation of T-synthase depends on its interaction with its chaperone Cosmc (Ju and Cummings 2010). Also known as C1GALT1C1, Cosmc is encoded by the X chromosome Xq24 in humans and Xc3 in mice (Ju et al. 2014; Xiang et al. 2022). Cosmc protects newly synthesized T-synthase from aggregation and degradation by the proteasome and is required for the proper folding and expression of T-synthase (Ju and Cummings 2002; Kudo et al. 2002; Müller et al. 2005; Ju et al. 2006). Without Cosmc, T-synthase is recognized and bound by glucose-regulating protein 78 (GRP78), which translocates T-synthase to the cytoplasm (Ni and Lee 2007; Xiang et al. 2022), where it is ubiquitinated and degraded (Ju et al. 2011; Ju et al. 2014). Cosmc is a critical component for T-synthase to function as there are no other chaperons that can interact with T-synthase in lieu of Cosmc (Ju et al. 2008a; Xiang et al. 2022). Cosmc and T-synthase have 26% amino acid sequence homology, and Cosmc is not expressed in invertebrates (Ju et al. 2011; Xiang et al. 2022).

Fig. 2.

Fig. 2

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Biosynthesis of Tn-antigen and sialyl Tn-antigen. T-synthase adds a galactose residue from UDP-Gal to Tn-antigen to form T-antigen. T-antigen is further glycosylated to form fully mature O-Glycans. Dysfunction in T-synthase leads to the accumulation of Tn-antigen and sialyl Tn-antigen. Created with BioRender.com.

The expression of Tn due to impaired function of T-synthase or Cosmc prevents elongation of the O-glycan, resulting in the dysregulation of numerous pathways and leading to the development of a myriad of diseases (Xiang et al. 2022). Any alterations in Cosmc or T-synthase can lead to abnormal Tn expression (Fig. 2) (Ju et al. 2011). Cosmc is critical in controlling and targeting several neoplastic and non-neoplastic diseases (Xiang et al. 2022).

Over the years, numerous approaches have been used to detect Tn antigen on purified proteins or its cellular expression (Ju et al. 2011). Structural elucidation of Tn-antigen by gas-liquid chromatography showed the presence of Ser/Thr linked terminal GalNAc on red blood cells isolated from Tn syndrome patients (Kulkarni et al. 2005; Ju et al. 2011). Tn detection approaches were developed based on plant lectins and anti-Tn antibodies (Springer et al. 1985; Kulkarni et al. 2005; Konska et al. 2006). Employing synthetic peptide acceptors and transferases, numerous chemoenzymatic strategies have generated synthetic Tn glycopeptide mimetics to investigate the Tn function (Wandall et al. 2010; Ju et al. 2011).

Tn expression in neoplastic and non-neoplastic diseases

Tn antigen is associated with dysregulation of numerous pathways required for normal physiological function (Xiang et al. 2022). Diseases caused by Tn expression can be divided into two categories: neoplastic and non-neoplastic diseases (Xiang et al. 2022). Neoplastic diseases are characterized by the growth of tumors or masses of cells, while an inflammatory environment characterizes non-neoplastic diseases without abnormal cellular proliferation. Numerous immune, inflammatory, viral, and neurodegenerative diseases have been associated with altered Tn expression (Xiang et al. 2022).

IgA nephropathy (IgAN) is among the most common glomerular pathologies resulting in end-stage kidney failure (Lai et al. 2016). Dysfunctional T-synthase cannot add galactose to GalNAc, resulting in hypoglycosylation of IgA1 (Lai et al. 2016). The IgG antibody responses against the hinge region Tn antigen of IgA1 results in circulating antigen–antibody complexes accumulating within the glomerular region of the kidney and causing glomerular damage (Kokubo et al. 1997; Hiki et al. 1999; Tomana et al. 1999). It has been shown that patients with IgA nephropathy have decreased expression of Cosmc (Lai et al. 2016). Patients with IgAN-associated renal insufficiency have increased concentrations of circulating IL-4 which downregulates the expression of Cosmc mRNA (Yamada et al. 2010). In addition, recent clinical studies have shown that Cosmc mRNA levels can be utilized as a biomarker for previse remission in IgAN patients (Akgul et al. 2023).

Tn Syndrome is caused by reduced Cosmc activity and the upregulation of Tn on the surface of red blood cells (Ju and Cummings 2005). The severity of Tn syndrome can vary between patients; some may be asymptomatic, while others may present with bleeding due to thrombocytopenia, red blood cell destruction, and anemia as a consequence of anti-Tn antibody production (Vainchenker et al. 1985; Berger 1999; Wang et al. 2012). Recently, germline Cosmc mutations have been identified as a multisystem chaperonopathy called COSMC-CDG (congenital disorder of glycosylation). Patients exhibit developmental delay, immunodeficiency, short stature, thrombocytopenia, and acute kidney injury (Erger et al. 2023).

In addition to these diseases, Alzheimer’s is a progressive neurodegenerative disease and another important pathology associated with increased Tn expression in the brain’s cortex (Lalezari et al. 2013; Van Cauwenberghe et al. 2016). Studies have demonstrated that the lack of Cosmc enhances Human T-Lymphotropic Virus Type 1 (HTLV-1) transmission between cells by affecting the glycosylation of lymphocyte cell surface antigens CD43 and CD45 (Mazurov et al. 2012; Xiang et al. 2022).

Mucin 1 (MUC1), expressed on epithelial cell surface is heavily O-glycosylated (Varki and Cummings 2009; Nath and Mukherjee 2014). MUC1 serves various important functions, such as supporting immune responses and protecting epithelial cells from infections (Brayman et al. 2004). The impaired Cosmc function in intestinal epithelium results in mucin hypoglycosylation and, therefore, inflammatory responses, intestinal instability, and changes in the expression and function of the mucin (Xiang et al. 2022). Research indicates that the hypoglycosylation of MUC1 leads to a decrease in the volume and viscosity of the mucosal surface of the intestinal tract, a crucial immune barrier (Machiels et al. 2014; Kudelka et al. 2016; Nishino et al. 2018). Furthermore, altered glycosylation of mucins in the airways of cystic fibrosis patients may augment the adhesion of pathogens such as Pseudomonas aeruginosa (Lamblin et al. 2001).

Tn expression in cancers such as the ovary, prostate, colon, lung, and breast have a poor prognosis and an increased likelihood of metastasis compared to those with lower Tn levels (Konno et al. 2002; Laack et al. 2002; Fernández Madrid et al. 2005; Ju et al. 2011). Mutations in Cosmc increase the expression of Tn in tumor tissues (Schietinger et al. 2006; Ju et al. 2008b; Ju et al. 2011). Tn-carrying MUC1 glycoproteins have also been linked to cancers such as breast, cervical, lung, bladder, hepatocellular, and colorectal cancer (Varki and Cummings 2009; Beatson et al. 2015; Lan et al. 2022). For example, when neoplastic changes occur in the colon, MUC1 becomes tumor-associated with an expression of truncated Tn and sialyl Tn antigens (Nath and Mukherjee 2014). The abnormal glycosylation of mucins and aberrant expression of Tn in cancer leads to metastasis and disruption of and evasion from the immune system (Codington et al. 1975; Carraway et al. 2001; Itoh et al. 2008; Carraway et al. 2009; Ju et al. 2011).

MGL-TN interaction

The interactions between MGL expressed by myeloid cells and GalNAc residues, which can be expressed on hypoglycosylated mammalian glycoproteins (i.e. Tn and STn antigens) and microbial products, have been observed in numerous neoplastic events and host-microbe interactions (Table 1) (Mortezai et al. 2013). Tumor-associated macrophages and Tn interactions were observed in one of the most aggressive brain tumors, glioblastoma, resulting in immune suppressive effects (Dusoswa et al. 2020). Additionally, human MGL is involved in recognizing tumor-associated MUC1, which expresses high levels of Tn antigen (Napoletano et al. 2007; Saeland et al. 2007). The interaction between tumor-associated MUC1 and MGL-expressing APCs has been associated with immune suppression in tumor microenvironments (Saeland et al. 2007; Allavena et al. 2010). Tn expression on cancer cells and their recognition by MGL and its effect on immunosurveillance has become an important research area. For example, Tn antigen on MUC1 colon cancer cells is recognized by MGL expressing macrophages and dendritic cells, and this interaction plays a key role in tumor progression (Saeland et al. 2007).

Table 1.

Representative terminal GalNAc-bearing glycans and their immune interactions.

GalNAc location Immune response Citations
Downregulated Upregulated
Self CD45 Effector Cells Teff – van Vliet et al. (2006)
Altered Self Tumor Associated MUC-1 Th1, CCL3 Th2, IL-10 Allavena et al. (2010)
Parasites Fasciola hepatica Th1 Th2, IL-10, TGFβ, TNFα, Treg Rodríguez et al. (2017)
Schistosoma mansoni Th1 Th2 van Liempt et al. (2007)
Trichuris suis IL-12, IL-6, TNFα Th2, OX40L, CXCL16 Klaver et al. (2013)
Bacteria Campylobacter jejuni IL-6 – van Sorge et al. (2009)
Neisseria gonorrhoeae – Th2, IL-4 van Vliet et al. (2009)
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Research has shown that increasing Tn expression on colorectal cancer cells in mice via modulation of Cosmc correlates with reduced CD8 T cell tumor infiltration (Cornelissen et al. 2020). Similarly, in a lung adenocarcinoma model expressing high levels of Tn, interactions with MGL-expressing APCs suppressed immune responses through the production of tolerogenic cytokines such as IL10 (Li et al. 2012; van Vliet et al. 2013; da Costa et al. 2021). Additionally, tumors expressing higher levels of Tn also expressed higher levels of immune regulatory markers such as FOXP3 and PDL1 (da Costa et al. 2021). Tn expression was correlated with increased tumor growth; this higher growth rate was abrogated when MGL-expressing immune cells were depleted (da Costa et al. 2021). However, various types of Tn-expressing tumor cells have significant differences in their ability to interact with DCs. Tn density and the protein backbone that carries Tn can affect MGL recognition and immune responses (Costa et al. 2022). Recent studies have demonstrated that IV injections of MGL can be a candidate for detecting Tn-expressing tumors in humans (Bulteau et al. 2022).

Tumor-associated macrophages (TAMs) promote carcinogenesis and tumor progression (Qian et al. 2009). TAM localization in tumor microenvironments has been linked to poor survival in hepatocellular carcinoma (Zhu et al. 2008). MGL-expressing immunoregulatory M2 macrophage subpopulations in the tumor microenvironment are correlated with tumor progression (Mantovani and Sica 2010; Qian and Pollard 2010; Solinas et al. 2010; Prokop et al. 2011).

Through binding to terminal GalNAc residues on CD45, MGL regulates T cell receptor signaling on the effector T cells (van Vliet et al. 2006; van Vliet et al. 2008). CD45 contains O-linked glycans, and approximately seven percent of CD45 glycans from human peripheral blood are terminal GalNAc residues recognized by MGL. This interaction is associated with the downregulation of effector T cell function and negatively altered T cell-dependent cytokine release. Reduced T cell proliferation regulated by Tn-MGL interaction may serve as a target for chronic inflammatory and autoimmune diseases (van Vliet et al. 2006).

MGL can identify infectious agents expressing terminal GalNAc residues, which numerous infectious agents can take advantage of in a process called glycan gimmickry (van Die and Cummings 2009). Infectious agents utilizing glycan gimmickry express host-like glycans to skew host immune responses to their benefit, creating favorable microenvironments for their proliferation (van Die and Cummings 2009). For example, Campylobacter jejuni has a terminal GalNAc residue on its lipo-oligosaccharides recognized by MGL (van Sorge et al. 2009). Additionally, Neisseria gonorrhoeae phenotype C expresses a terminal GalNAc residue that is recognized by MGL, skewing the host immune response toward the Th2 pathway (van Vliet et al. 2009). Both human and murine MGL can recognize infectious agents such as filoviruses, the human worm parasite Schistosoma mansoni, and a pig whipworm parasite named Trichuris suis (van Liempt et al. 2007; Meevissen et al. 2012; Klaver et al. 2013). The highly glycosylated envelope protein of filoviruses is a ligand for MGL, and it increases infectivity by promoting viral attachment (Takada et al. 2004; van Vliet et al. 2008). The latest studies show that Fasciola hepatica, a parasite in bile ducts, has GalNAc-Ser/Thr on parasite glycoproteins (Freire et al. 2003). Immune surveillance of these infections after recognition of Tn by MGL results in suppression of Th1 response and release of regulatory cytokines mediating anti-inflammatory effects (Rodríguez et al. 2017).

Summary and outlook

Protein-carbohydrate interactions are critical in immune regulation and activation (Paschall et al. 2023). Dysfunction or dysregulation of T-synthase, or its chaperone Cosmc, prevents glycan elongation and results in the truncated Tn antigen (Ju et al. 2011). Quantifying Tn expression offers a new method to monitor disease progression and explore tumor and infectious microenvironments. Tn antigen is specifically recognized by the C-type lectin MGL, expressed by macrophages and immature dendritic cells (van Vliet et al. 2008). MGL recognition of Tn antigen modulates immune responses in cancer, infectious disease, and non-neoplastic diseases. This interaction is associated with tumor metastasis, poor prognosis, and immune suppression (da Costa et al. 2021). Numerous infectious diseases are capable of utilizing immune suppression through molecular mimicry. For example, helminths synthesize antigenic glycans with terminal GalNAc residues that mimic Tn antigen to evade host recognition and immune responses. The discovery of glycan gimmickry elucidated an important mechanism parasites use to evade host immune responses and opened the door for different approaches to disease detection and vaccine development (van Die and Cummings 2009). The presence of bacteria and parasites exploiting MGL-induced immunoregulation (as demonstrated in Table 1) raises the question of the evolutionary necessity for MGL’s specificity toward the Tn antigen. Regulation of effector T cells by antigen-presenting cells via interaction of MGL with the Tn antigen on CD45 (van Vliet et al. 2006; van Vliet et al. 2008) hints at MGL’s role in immune function during homeostasis. Another example of MGL’s role as a key immune mediator was demonstrated in MGL-expressing dermal dendritic cells that drive T helper 2 cell-mediated immunity (Kumamoto et al. 2013). MGL, as an important immunoregulatory surface receptor, is an emerging topic that requires further investigation. The regulation of the O-glycosylation pathways in immune function may lead to new immune mechanisms induced by protein-carbohydrate interactions, including MGL-Tn interactions. Our extensive knowledge of how cancer leverages aberrant protein glycosylation may guide us in discovering previously uncharacterized immune regulatory pathways.

Inhibition or antagonism of MGL significantly alters the progression of numerous inflammatory and neoplastic diseases (Kumamoto et al. 2016), offering a potential target for developing new therapeutics. Tn vaccines (Li et al. 2009) may elicit immune responses against cells that have upregulated Tn expression, which has implications in neoplastic, infectious, and non-neoplastic diseases. Since MUC1 is overexpressed in numerous carcinomas, it is an attractive target for cancer vaccine development. Studies have shown that aberrantly glycosylated MUC1, bearing truncated saccharides such as Tn antigen, function as a trivalent vaccine and induce a stronger therapeutic response in a humanized mouse model of mammary cancer (Lakshminarayanan et al. 2012). In another study, MGL was targeted with specifically generated GalNAc-enriched MUC1, which induced higher titers of anti-Tn MUC1 antibodies compared to the MUC1 alone. These anti-MUC1 antibodies recognize MUC1-positive breast cancer cells (Gabba et al. 2023). Additionally, anti-Tn-MUC1 CAR T cells have been successful in controlling tumor growth in mouse models of leukemia and pancreatic cancer (Posey Jr et al. 2016). Advances have also been made in the early detection of cancer using anti-Tn antibody microarrays (ATAM), which are capable of detecting Tn-containing glycopeptides in serum and stool samples (Kudelka et al. 2023).

Elucidation of the interaction between MGL and Tn has offered new insights into immunosuppression, tumor, and infectious microenvironments. Future studies addressing the structural, cellular, and systemic aspects of MGL-Tn interaction will help reveal new immune mechanisms. For example, the immunoregulatory ligands released in conjunction with MGL-Tn interactions are yet to be fully profiled, and the receptors they bind to and the immune mechanisms initiated are still largely unknown. Discovering these immune pathways and their mechanisms could lead to the development of new drug targets to manage or treat human diseases.

Author contributions

Berna Tumoglu (Conceptualization [equal], Writing—original draft [lead], Writing—review & editing [supporting]), Aidan Keelaghan (Data curation [supporting, Writing—original draft supporting], Writing—review & editing [supporting]), and Fikri Avci (Conceptualization lead], Funding acquisition [lead], Project administration [lead], Supervision [lead], Validation [lead], Writing —original draft [equal], Writing—review & editing [lead])

Funding

National Institute of Allergy and Infectious Diseases, (Grant/Award Number: R01AI123383, R01AI152766, R41AI157287).

 

Conflict of interest statement: The authors declare no conflict of interest with the contents of this article.

Data availability

All data contained within the manuscript.

Contributor Information

Berna Tumoglu, Department of Biochemistry, Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, United States.

Aidan Keelaghan, Department of Biochemistry, Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, United States.

Fikri Y Avci, Department of Biochemistry, Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, United States.

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