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Characterization of a novel glycolipid with a difucosylated H-antigen in human blood group O erythrocytes with monoclonal antibody HMMC-1 and its detection in human uterine cervical carcinoma tissues

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Abstract

Humanized monoclonal antibody HMMC-1 established by immunizing transchromosomal mice with a human uterine endometrial cancer cell line has been found to react with the H-antigen carried on core l O-glycans through cotransfection of glycosyltransferases for O-glycans and inhibition of antibody-binding with synthetic oligosaccharides. However, direct binding analysis of an antibody against glycosphingolipids from human erythrocytes with different ABO blood groups revealed that it was able to bind selectively with polar glycolipids in blood group O, but not blood group A, B and AB erythrocytes. Unexpectedly, typical monofucosylated H-glycolipids, IV2Fucα-nLc4Cer and VI2Fucα-nLc6Cer, which are the precursors for A and B-glycolipids, and were present not only in blood group O, but also A, B and AB-erythrocytes, were not the antigens for the HMMC-1 antibody. The antigen comprised less than 0.001% of the total glycolipids in blood group O-erythrocytes, and was purified by conventional silica gel column chromatography. Structural determination by permethylation, GC-MS, and ESI-TOFMS demonstrated that the structure was a novel glycolipid with a difucosylated H-antigen, Fucα1–2Galβ1-4GlcNAcβ1–3Gal(2-1αFuc)β1-4GlcNAcβ1–3Galβ1-4GlcNAcβ1–3Galβ1-4Glcβ1–1’Cer, VI2,VIII2(Fucα)2-nLc8Cer, whose terminal difucosylated structure was the epitope of the HMMC-1 antibody. The HMMC-1 glycolipid was detected in five out of 29 tissues from patients suffering from uterine cervical carcinomas, irrespective of their ABO-blood groups.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Ohashi Hospital, Toho University, 2-22-36, Ohashi, Meguro-ku, Tokyo, 153-8515, Japan

    Kyoko Tanaka

  2. Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan

    Akemi Suzuki

  3. Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Daisuke Aoki

  4. Laboratory of Animal Models for Human Diseases, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Asagi-Saito, Osaka, Ibaraki, 567-0085, Japan

    Masao Iwamori

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  1. Kyoko Tanaka
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  2. Akemi Suzuki
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  3. Daisuke Aoki
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  4. Masao Iwamori
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Correspondence to Masao Iwamori.

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Abbreviations used

The nomenclature for glycolipids is based on the recommendations of the IUPAC-IUB Commission on Biochemical Nomenclature [1].

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Tanaka, K., Suzuki, A., Aoki, D. et al. Characterization of a novel glycolipid with a difucosylated H-antigen in human blood group O erythrocytes with monoclonal antibody HMMC-1 and its detection in human uterine cervical carcinoma tissues. Glycoconj J 36, 219–226 (2019). https://doi.org/10.1007/s10719-019-09873-3

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  • DOI: https://doi.org/10.1007/s10719-019-09873-3

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