MUC1 (12-20) peptide (LLLLTVLTV) – Immunology – Antigens/Epitotes/Pools/Librairies

MUC1 (Mucin 1) protein is a type 1 transmembrane glycoprotein characterized by a large extracellular domain. This domain contains a variable number (up to 120) of 20-amino acid repeat sequences (PDTRPAPGSTAPPAHGVTSA). But also,a high glycosylation level on serine and threonine residues within each tandem repeat1. MUC1 protein is expressed at the apical part of secretory epithelial cells. It is involved in the protection of epithelial surfaces as well as intracellular signalling. However,the aberrant MUC1 overexpression along with the modification of its glycosylation pattern has been associated with several carcinomas. Including more than 90% of breast and pancreas cancers as wells as hematologic malignancies such as multiple myelomas and lymphomas2. These hallmarks make MUC1 highly immunogenic when its expressed in tumor cells. But also,an attractive and broadly applicable target for cancer inmunotherapy. MUC1 has indeed prompted research to develop T-cell vaccine strategies capable of inducing MUC1-specific cytotoxic T lymphocyte responses in cancer patients upon immunization with a MUC1 antigenic epitope. MUC1 epitopes presented by the HLA-A*0201 molecules are most studied. The capacity of MHC-restricted cytotoxic T lymphocytes (CTLs) to recognize MUC1-expressing tumor cells is assessed to validate the epitope1. The HLA-A2-restricted MUC1 (12-20) peptide (LLLLTVLTV) derives from the leader sequence of MUC1 protein. MUC1 (12-20) has demonstrated the ability to induce MUC1-specific CTL responses3. Nevertheless,the immunodominant region of the tandem repeat domain (amino acids 950– 958,STAPPVHNV) has been also recognized by MUC1-specific CTLs in an antigen-specific and HLA-A2-restricted fashion3. The half maximal inhibitory concentrations (IC50) for the MUC1 (950– 958) peptide and the MUC1 (12-20) peptide have been determined. Using a competitive peptide inhibition assay IC50 results were 10.13 µg/ml and 10.89 µg/ml,respectively2. Hence,these two peptides fall within the IC50 range for “medium binders”. Recently,it has been reported that optimization of MUC1 (950– 958) peptides showed higher binding affinities. This optimization through specific amino acid substitution and/or aberrant glycosylation showed IC50 ranging from 0.34 to 1.68 µg/ml. Thus,modified peptides can be considered as « high-affinity binders » which may serve for developing more efficient MUC1-specfic cancer vaccines2.

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