A neutralizing epitope of human immunodeficiency virus type 1 has homologous amino acid sequences with the active site of inter-alpha-trypsin inhibitor.
A neutralizing epitope (epitope beta) of the HTLV-IIIB strain of HIV-1 was mapped to 24 amino acids of an external envelope glycoprotein (gp120) using a neutralizing monoclonal antibody (0.5 beta) and hetero-antisera against synthetic peptides encoding gp120. Proteins that have homologous sequences with epitope beta were sought from a databank of protein sequences to assess biological features of epitope beta. The results showed that epitope beta was found to have homologous sequences to inter-alpha-trypsin inhibitor (ITI). The homologous region of ITI included the active site of the protein. Synthesized peptides including epitope beta were good substrates for trypsin, because these peptides inhibited trypsin activities in a competitive manner (Ki = 24.5 microM). Human urinary trypsin inhibitor (UTI), a protein indistinguishable from ITI, as well as synthetic peptides including epitope beta inhibited syncytium formation caused by the LAV-1-infected CCRF-CEM and uninfected Molt-4 cells in a dose-dependent manner (0.1-1 mM). These findings suggest that epitope beta of HIV-1 could be substrate of protease upon HIV-1 infection and also suggest that protease inhibitory activity of epitope beta may play a role in the pathophysiology of HIV-1-infected individuals.
Koito
A
A
Second Department of Internal Medicine, Kumamoto University Medical School, Japan.
Hattori
T
T
Murakami
T
T
Matsushita
S
S
Maeda
Y
Y
Yamamoto
T
T
Takatsuki
K
K
D000510:Alpha-Globulins / Q000737:chemistry* / Q000276:immunology; D000595:Amino Acid Sequence; D001665:Binding Sites; D000939:Epitopes / Q000737:chemistry; D015488:HIV Antigens / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D012689:Sequence Homology, Nucleic Acid; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000276:immunology
D000510:Alpha-Globulins; D000939:Epitopes; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D014361:Trypsin Inhibitors; C011877:inter-alpha-inhibitor