A fucose residue can mask the MUC-1 epitopes in normal and cancerous gastric mucosae.
MUSE11, DF3 and SM3 MAbs react with a synthetic peptide of 20 amino-acids: VTSAPDTRPAPGSTAPPAHG. This sequence is a tandem repeat domain of the mucin-type glycoprotein coded by the muc-1 gene. MUSE11 and DF3 MAbs immunoreact strongly with mucus cells of the normal surface gastric epithelium of Le(a+b-) non-secretors, but in spite of the peptidic nature of the recognized epitope, the same tissue of Le(a-b+) secretors reacts only after treatment with alpha-fucosidase. These reactions are inhibited by the PNA lectin, which recognizes the T disaccharide antigen (beta Gal 1-3 alpha GalNAc), suggesting that the peptide epitope may be close to the T-saccharide structure. The SM3 MAb reacted on the surface gastric epithelium of all individuals after a more drastic deglycosylation using 20 mM periodate. Computer modeling of the MUC-1 immunoreactive glycopeptide containing the H type-3 trisaccharide alpha Fuc 1-2 beta Gal 1-3 alpha GalNAc- bound to the threonine of the PDTRP-pentapeptide shows that the peptide epitope might be masked when the fucose is positioned over the arginine. Thus, a single fucose linked to the T structure could mask the MUC-1 epitopes. In gastric adenocarcinomas, MUSE11 and SM3 epitopes are expressed in 75% (25/33) and 9% (3/33) respectively, while, after partial deglycosylation by periodate treatment, they are positive in 100% (33/33) and 70% (23/33) of cases, respectively.
Bara
J
J
Mucin Immunochemistry Laboratory, IRSC, Villejuif, France.
Imberty
A
A
Pérez
S
S
Imai
K
K
Yachi
A
A
Oriol
R
R
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D005643:Fucose / Q000737:chemistry / Q000276:immunology*; D005753:Gastric Mucosa / Q000737:chemistry / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins / Q000737:chemistry / Q000276:immunology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid; D013274:Stomach Neoplasms / Q000737:chemistry / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D008562:Membrane Glycoproteins; D018396:Mucin-1; D009077:Mucins; D009363:Neoplasm Proteins; D005643:Fucose