Human antibodies to immunodominant C5 region of HIV-1 gp120 cross-react with HLA class I on activated cells.
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.
de Santis
C
C
DIBIT, Dipartimento di Ricerca Biologica e Tecnologica, Ospedale San Raffaele, Milan, Italy.
Lopalco
L
L
Robbioni
P
P
Longhi
R
R
Rappocciolo
G
G
Siccardi
A G
AG
Beretta
A
A
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D002846:Chromatography, Affinity; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015395:Histocompatibility Antigens Class I; D007143:Immunoglobulin Heavy Chains