A fucose residue can mask the muc‐1 epitopes in normal and cancerous gastric mucosae

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Abstract
MUSE II, DF3 and SM3 MAbs react with a synthetic peptide of 20 amino-acids: VTSAPDTRPAPGSTAPPAHG. This se quence is a tandem repeat domain of the mucin-type glycopro tein coded by the muc-1 gene. MUSE II and DF3 MAbs immuno react 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 α-fucosi dase. These reactions are inhibited by the PNA lectin, which recognizes the T disaccharide antigen (βGall-3αGalNAc), sug gesting that the peptide epitope may be close to the T-saccha ride 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-I immunoreactive glycopeptide containing the H type-3 trisaccha ride αFucl-2βGall-3αGalNAc- 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-I epitopes. In gastric adenocarcinomas, MUSEII and SM3 epi topes 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.