Localization of B-cell stimulatory activity of HIV-1 to the carboxyl terminus of gp41.
Patients with AIDS are known to have B-cell hyperactivity. We have previously demonstrated that an extract of HIV-1 could induce differentiation of peripheral blood B lymphocytes of healthy volunteers into immunoglobulin-secreting cells. In an attempt to delineate the B-cell stimulatory subregion in HIV-1, we have investigated the influences of native glycoproteins and recombinant proteins of the envelope. The complete envelope glycoprotein, gp160 and a recombinant protein in the carboxyl terminal region of gp41 termed PE-8 were effective in inducing terminal differentiation of normal peripheral blood B lymphocytes and did so in a T-lymphocyte-dependent manner. The activity was not present in the native exterior envelope glycoprotein, gp120 and several other recombinant proteins, viz PE-2 an PE-3, which are in the amino terminal region of gp120 or in env-9, a protein in the junctional region of gp120 and gp41. Polyclonal and monoclonal antibodies directed to diverse regions of the envelope abrogated the influence of gp160. The PE-8-induced B-cell differentiation was abrogated by goat anti-gp160 antibody but not by goat anti-gp120 antibody or monoclonal antibody to the amino terminal of gp41. These studies suggest that a putative polyclonal B-cell stimulatory epitope of HIV-1 is located in the carboxyl end of the envelope glycoprotein.
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY.
N
N
Chirmule
V S
VS
Kalyanaraman
C
C
Saxinger
F
F
Wong-Staal
J
J
Ghrayeb
S
S
Pahwa
D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D015686:Gene Products, env / Q000276:immunology / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000494:pharmacology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000276:immunology / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000494:pharmacology*
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins