title: Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class I alpha 1 peptide-binding domain.
abstract: Molecular mimicry of major histocompatibility (MHC) antigens by viral glycoproteins has been suggested as one of the possible mechanisms of induction of an autoimmune response by human immunodeficiency viruses. A monoclonal antibody (M38) was previously shown to bind to both human immunodeficiency virus type 1 (HIV-1) gp120 and beta-2 microglobulin-free HLA class I heavy chains encoded by an HLA C allele. Using HLA C recombinant proteins and synthetic peptides, the M38 class I binding site was mapped to a stretch of 44 amino acids of the alpha 1 domain. The amino acid residues recognized are clustered in two non-contiguous regions at positions 66-69 (KYKR) and 79-82 (RKLR) shared by almost all HLA C alleles. On HIV-1 gp120, M38 binds to two non-contiguous sequences (KYK and KAKR) at positions 490-492 and 505-508 located at the edges of a large hydrophobic region that is apparently involved in binding the transmembrane glycoprotein gp41. The C-terminal gp120 M38-reactive region (KAKR) lies within the immunodominant sequence APTKAKRRVVQREKR, against which the majority of HIV-infected individuals produce antibodies. The results indicate that a functionally important region of HIV-1 gp120 shares similar amino acid sequence motifs with the antigen recognition site of most HLA class I C alleles. The molecular mimicry may be the basis for autoimmune responses in HIV infection.
authors.affiliation: DIBIT, Dipartimento di Ricerca Biologica e Tecnologica, Ospedale San Raffaele, Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Lopalco
authors.forename: C
authors.initials: C
authors.lastname: De Santis
authors.forename: R
authors.initials: R
authors.lastname: Meneveri
authors.forename: R
authors.initials: R
authors.lastname: Longhi
authors.forename: E
authors.initials: E
authors.lastname: Ginelli
authors.forename: F
authors.initials: F
authors.lastname: Grassi
authors.forename: A G
authors.initials: AG
authors.lastname: Siccardi
authors.forename: A
authors.initials: A
authors.lastname: Beretta
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D003429:Cross Reactions; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015236:HLA-C Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D015236:HLA-C Antigens; D010446:Peptide Fragments; D011994:Recombinant Proteins