Human antibodies to immunodominant C5 region of HIV-1 gp120 cross-react with HLA class I on activated cells
Autor: | Renato Longhi, Piera Robbioni, Lucia Lopalco, Antonio G. Siccardi, Alberto Beretta, Giovanna Rappocciolo, Claudio De Santis |
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Předmět: |
medicine.drug_class
T-Lymphocytes Blotting Western Molecular Sequence Data Immunology Enzyme-Linked Immunosorbent Assay Human leukocyte antigen Cross Reactions HIV Antibodies HIV Envelope Protein gp120 Lymphocyte Activation Monoclonal antibody Gp41 Chromatography Affinity Epitope Epitopes Viral envelope Western blot Virology medicine Humans Amino Acid Sequence chemistry.chemical_classification biology medicine.diagnostic_test Histocompatibility Antigens Class I Antibodies Monoclonal virus diseases Amino acid Infectious Diseases chemistry HIV-1 biology.protein Antibody Immunoglobulin Heavy Chains |
Zdroj: | Scopus-Elsevier |
Popis: | Cross-reactive antibodies to HLA class I and HIV-1 gp120 were detected in the sera of HIV-1-positive individuals, and were found to share the same epitope specificity as a gp120-HLA class I cross-reactive monoclonal antibody (M38). The amino acid residues of HLA recognized by both M38 and the patient antibodies occur as a clustered pair in the HLA-C alpha 1 domain. These sequences (KYKR and RKLR) are shared by almost all HLA-C alleles and are available to antibody binding only on beta 2-microglobulin-dissociated HLA heavy chains expressed on activated cells. Similar to M38, the antibody-binding sites on HIV-1 gp120 were mapped to two noncontiguous stretches of amino acids (KYK and KAKR), which flank a hydrophobic area of the immunodominant C5 region involved in gp41 binding. Serum antibodies immunoaffinity purified on synthetic HLA and gp120 peptides representing the M38-reactive regions were shown to bind to both HLA and gp120 in Western blot, as well as to membrane-bound HLA heavy chains, and to exhibit selective complement-mediated lysis of activated T cells. No serum antibodies could be detected that bind to the gp120 C5 region (peptide IEPLGVAPT) flanked by the two HLA-like sequences. |
Databáze: | OpenAIRE |
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