title: HIV-1 gp120/V3-derived epitopes promote activation-induced cell death to superantigen-stimulated CD4+/CD45RO+ T cells.
abstract: The third hypervirable (V3) domain of the HIV-1 envelope glycoprotein gp120 has been implicated in HIV pathogenesis via co-receptor usage of chemokine receptors CCR5 and CXCR4. As the protagonist cell populations in the asymptomatic phase of HIV-1 infection are infected macrophages and effector/memory (CD45RO+) CD4+ T cells that express CCR5, we established an in vitro model using human primary monocyte-derived macrophages and lymphocytes to investigate the role of V3 in affecting antigen presentation. We used staphylococcal enterotoxin A (SEA) as a superantigen at a low concentration of 1ng/ml, to activate naïve CD4+ T cells. Exposure of cells to SEA and lipoV3-liposomes increased the percentage of CD4+/CD45RO+/CCR5+ T cell population as compared to cells treated with SEA and plain liposomes. A consequent decrease of the percentage of CD4+/CD45RO+/CXCR4+ subset was observed. The V3-mediated activation was competitively inhibited by soluble V3-derived peptides with higher cationic charge. V3 enhanced also apoptosis as demonstrated by flow cytometry and intracellular calcium ion assays. These results reinforce the postulation that V3 alters the antigen presentation function itself, independent of specific antigens, thus leading to an enhanced activation-induced cell death (AICD) of responding T cells.
authors.affiliation: Department of Applied Biochemistry and Immunology, Institute of Molecular Biology and Biotechnology, Vassilika Vouton, Heraklion, Crete, Greece.
authors.forename: Filippos
authors.initials: F
authors.lastname: Porichis
authors.forename: Zaharenia
authors.initials: Z
authors.lastname: Vlata
authors.forename: George
authors.initials: G
authors.lastname: Hatzidakis
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
authors.forename: Elias
authors.initials: E
authors.lastname: Krambovitis
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000097:blood / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism*; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D018089:Superantigens / Q000494:pharmacology
chemical_list: D004768:Enterotoxins; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D008081:Liposomes; D010446:Peptide Fragments; D019713:Receptors, CCR5; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; D017493:Leukocyte Common Antigens; D002118:Calcium