FACTORS AFFECTING EXPRESSION OF GLYCOLIPID TUMOR-ANTIGENS - INFLUENCE OF CERAMIDE COMPOSITION AND COEXISTING GLYCOLIPID ON THE ANTIGENICITY OF GANGLIOTRIAOSYLCERAMIDE IN MURINE LYMPHOMA-CELLS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (10) , 4997-5005
Abstract
Gangliotriaosylceramide (Gg3Cer) was previously described as a tumor-associated antigen in murine L5178Y lymphoma. The major factors affecting the expression of Gg3Cer at the surface of various clones of L5178Y lymphoma are described. Of 26 sublines that were recloned, 6 cell lines showing different degrees of Gg3Cer expression at the cell surface were used for analysis of the glycolipid composition as related to its cell surface antigenicity. Three remarkable correlations between glycolipid composition and the antigenicity of Gg3Cer were found: high-expressor sublines were characterized by a large proportion of a unique molecular species of Gg3Cer having .alpha.-hydropalmitic and in its ceramide moiety in striking contrast to low expressors which did not contain this molecular species; low expressors contained a large quantity of ganglio-N-tetraosylceramide (Gg4Cer) and NeuAc.alpha.2 .fwdarw. 3Gal.beta.1 .fwdarw. 3GalNAc-.beta.1 .fwdarw. 4Gal.beta.1 .fwdarw. 4Glc.beta.1 .fwdarw. 1Cer(GM1b) gangliosides, whereas these glycolipids were almost absent in high-expressor clones; and nonexpressors, which were converted from the high expressors in vivo through immunotherapy with the monoclonal antibodies to Gg3Cer, contained a large quantity of ganglio-N-tetraosylceramide and NeuAc.alpha.2 .fwdarw. 3Gal.beta.1 .fwdarw. 3GalNAc.beta.1 .fwdarw. 4Gal.beta.1 .fwdarw. 4Glc.beta.1 .fwdarw. 1Cer. The nonexpressors should have an induced enzyme system to metabolize Gg3Cer to ganglio-N-tetraosylceramide and NeuAc.alpha.2 .fwdarw. 3Gal.beta.1 .fwdarw. 3GalNAc.beta.1 .fwdarw. 4Gal.beta.1 .fwdarw. 4Glc.beta.1 .fwdarw. 1Cer. Three factors, i.e., ceramide composition, coexisting glycolipids, and an antibody-dependent glycolipid change, are therefore important in determination of glycolipid antigenicity and antigen modulation by antibodies. The ceramide composition may affect glycolipid organization in membranes, and the coexisting glycolipid having a longer carbohydrate chain may mask the accessibility of antibody to the antigenic glycolipid. The antigenic modulation by the action of the antibody in vivo may be based on activation of a new glycosyltransferase.

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