Synergism between HIV gp120 and gp120-specific antibody in blocking human T cell activation.
The human immunodeficiency virus (HIV) binds to CD4-positive cells through interaction of its envelope glycoprotein (gp120) with the CD4 molecule. CD4 is a prominent immunoregulatory molecule, and chronic exposure to antibody against CD4 (anti-CD4) has been shown to cause immunodeficiency in mice. T cell-dependent in vitro immune responses can also be inhibited by anti-CD4. Experimental findings reported here indicate that CD4-bound gp120 attracts gp120-specific antibodies derived from the blood of HIV-seropositive individuals to form a trimolecular complex with itself and CD4. Thus targeted to CD4, the gp120-specific antibody functions as an antibody to CD4; it cross-links and modulates the CD4 molecules and suppresses the activation of T cells as measured by mobilization of intracellular calcium (Ca2i+). The synergism between gp120 and anti-gp120 in blocking T cell activation occurs at low concentrations of both components. Neither gp120 nor anti-gp120 inhibits T cell activation by itself in the concentrations tested.
Mittler
R S
RS
Bristol-Myers Company, Wallingford, CT 06492.
Hoffmann
M K
MK
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120; D006801:Humans; D007152:Immunologic Capping; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012191:Retroviridae Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D011948:Receptors, Antigen, T-Cell; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D002118:Calcium