Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class I alpha 1 peptide-binding domain.
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.
Lopalco
L
L
DIBIT, Dipartimento di Ricerca Biologica e Tecnologica, Ospedale San Raffaele, Milano, Italy.
De Santis
C
C
Meneveri
R
R
Longhi
R
R
Ginelli
E
E
Grassi
F
F
Siccardi
A G
AG
Beretta
A
A
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
D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D015236:HLA-C Antigens; D010446:Peptide Fragments; D011994:Recombinant Proteins