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 huma n 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 alpha1 domain. T he amino acid residues recognized are clustered in two non-contiguous regions at positions 66-69 (KYKR) and 79-82 (RKLR) shared by almost al l HLA C alleles. On HIV-1 gp120, M38 binds to two non-contiguous seque nces (KYK and KAKR) at positions 490-492 and 505-508 located at the ed ges of a large hydrophobic region that is apparently involved in bindi ng the transmembrane glycoprotein gp41. The C-terminal gp120 M38-react ive region (KAKR) lies within the immunodominant sequence APTKAKRRVVQR EKR, against which the majority of HIV-infected individuals produce an tibodies. The results indicate that a functionally important region of HIV-1 gp120 shares similar amino acid sequence motifs with the antige n recognition site of most HLA class I C alleles. The molecular mimicr y may be the basis for autoimmune responses in HIV infection.