Galactose receptors and presentation of HIV envelope glycoprotein to specific human T cells.
Recognition of viral Ag and of the envelope glycoprotein of HIV (gp120) in particular by human Th cells is critical in the immune response to the viral Ag which includes antibody production and generation of cytotoxic cells. Procedures to increase antigenicity of gp120 are highly desirable in a vaccine perspective. Therefore, to induce activation of gp120-specific T cells by a liminal dose of Ag we enhanced uptake of gp120 by exploiting the galactose receptors on APC. Terminal sialic acid residues were removed by neuraminidase treatment from the carbohydrate side chains of the heavily glycosylated gp120. Galactose residues were exposed and hence recognized by galactose receptors on APC. The experiments demonstrated that 1) human monocytes and dendritic cells, but not cells of the B lineage, bear galactose receptor; 2) galactose receptors are indeed involved because enhanced presentation is inhibited by galactose and acetylgalactosamine and competed for by other asialoglycoproteins; 3) galactose receptors mediate internalization of Ag in intracellular compartments that intersect the processing and presenting pathways, resulting in activation of specific T cells; 4) antigenicity of gp120 for specific T cells can be enhanced by the exposure of galactose residues.
Manca
F
F
Department of Immunology, University of Genoa, San Martino Hospital, Italy.
D000938:Antigen-Presenting Cells / Q000502:physiology; D001212:Asialoglycoproteins / Q000276:immunology; D002478:Cells, Cultured; D005690:Galactose / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000502:physiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D001212:Asialoglycoproteins; D015699:HIV Envelope Protein gp120; D011956:Receptors, Cell Surface; C039707:galactose receptor; D005690:Galactose