The tumour-protective ability of mucins against the host immune response
is embedded on its structural peculiarity. The interested readers are directed to refer excellent reviews on mucin structural biology [29, 30] for a comprehensive account on this subject. Mucins can be both immunostimulatory and immunosuppressive in their effects. MUC-1, for example, is a highly immunogenic tumour-associated antigen (TAA) that provides a unique immune system access to the MUC-1 over expressing breast, pancreas and ovarian carcinomas . If poorly glycosylated on its VNTR , it elicits humoral  and cellular immune responses , and the major epitope recognized by the antibodies is the PDTRPAP sequence with its o-glycosylation on its threonine residues [35, 36]. Interestingly, antigen processing of MUC-1 by dendritic cells (DC) or in human immunoproteasomes in vitro retains its o-linked glycans on its repeat domains. Its JNK inhibitor cost 20 amino acid tandem repeat (TR) posses three specific cleavage sites, being processed by human cathepsin L in low-density endosomes in a manner that is sensitive to o-glycosylation positions. Proteolysis of Thr-3-Ser-4 peptide bond in the TR does not occur if either amino acid is o-glycosylated, and this MK-1775 manufacturer masking of cleavage site is responsible for inertness of tumour-associated MUC-1 glycoforms to effective DC processing . Further, it has been found that the
processed SAPDT(GalNAc)RPAPG decameric glycopeptide containing a single sugar (GalNAc) binds strongly Liothyronine Sodium to MHC class I allele HLA A*0201, whereas the same sequence glycosylated with the disaccharide Gal-GalNAc does not bind at all . Processed MUC-1 TRs can use GalNAc to anchor on to the c-pocket of HLA class I (H-2 kb) molecule, and the number of
anchors subsequently influences the affinity with which MUC-1 is presented on to the MHC class I . Low-affinity binding of the 9-mer MUC-1 peptide sequences (APDTRPA and STAPPAHGV) on to the HLA-A2 is partly due to the lack of high-affinity consensus motif and to the under glycosylation , and only HLA-A11 binding is close to the immunogenic value . Nevertheless, cytotoxic T lymphocytes (CTLs) generated against it are highly active and could lyse the human breast cancer cells expressing MUC-1 . Breast cancer cells therefore escape from autologous CTLs by expressing MUC-1-related antigenic epitopes more weakly or by modulating its antigenicity . Complete loss of MUC-1 is also observed in some breast tumour cell lines that are unresponsive or resistant to CTL cytotoxicity and characterized with antitumor immunity . Conversely, downregulation or loss of HLA class I expression in MUC-1 or c – erbB2 overexpressing NSCLC cells confer poor prognosis of the disease  and the mice lacking MHC- Class I made weak CTL response . Dendritic cells (DCs) form a crucial link between innate and adaptive immunity leading to specific T cell activation.