Identification of CD4 and major histocompatibility complex functional peptide sites and their homology with oligopeptides from human immunodeficiency virus type 1 glycoprotein gp120: role in AIDS pathogenesis
| Autor: | JP Mbika, A Astgen, Jean-François Zagury, Claude Carelli, Jacky Bernard, W Issing, O. Picard, A Lachgar, Ammar Achour, Lat S. Fall |
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| Rok vydání: | 1993 |
| Předmět: |
Cytotoxicity
Immunologic Cellular immunity T-Lymphocytes Molecular Sequence Data Enzyme-Linked Immunosorbent Assay Human leukocyte antigen HIV Envelope Protein gp120 Major histocompatibility complex Monocytes Mice Immune system Antigens CD HLA Antigens Animals Humans Cytotoxic T cell Amino Acid Sequence Peptide sequence Acquired Immunodeficiency Syndrome HLA-D Antigens Multidisciplinary Sequence Homology Amino Acid biology Macrophages Envelope glycoprotein GP120 Virology Cell biology CD4 Antigens HIV-1 biology.protein Antibody Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 90:7573-7577 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.90.16.7573 |
| Popis: | CD4 molecules interact with class II major histocompatibility complex molecules as a critical costimulatory signal in CD4+ cell immune activation. CD4 also recognizes a specific region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 forming a binding site for early stages of HIV-1 infection. We designed two software packages, AUTOMAT and CRITIC, which allowed us to identify similarities between regions of HIV-1 proteins and immunoregulatory protein sequences stored in data banks. In this report we have characterized (i) a pentapeptide, SLWDQ, found in both CD4 and HIV-1 gp120, which surprisingly had remained undetected in these two well-studied molecules until now, and (ii) an HLA sequence corresponding to the putative functional site of H2 I-A. We found that a region of gp120 (residues 254-263) known to be similar to a sequence in HLA class II beta chain overlaps this functional region. We showed experimentally that these two CD4 and HLA peptide segments inhibit CD4+ cell immune activation. There is strong inhibition (50% up to 80%) of immune activation by SLWDQ-containing gp120 segments and a lesser inhibition by the gp120 HLA-homologous segment. In addition, we found that SLWDQ induced in HIV-1-infected individuals a humoral (antibody) and cellular (cytotoxic T lymphocyte) immune reaction. We propose that these HIV-1 gp120 segments, together with the known CD4-binding region, may contribute to the HIV-1-induced immunosuppression by two mechanisms affecting CD4-HLA interaction during T-cell immune activation: autoimmune reaction toward CD4 and direct interference with the CD4-HLA costimulatory signal inducing CD4+ cell anergy with, as a consequence, generation of immunosuppression. |
| Databáze: | OpenAIRE |
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