Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class I α1 peptide-binding domain
✍ Scribed by Lucia Lopalco; Claudio de Santis; Raffaella Meneveri; Renato Longhi; Enrico Ginelli; Fabio Grassi; Antonio G. Siccardi; Alberto Beretta
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 633 KB
- Volume
- 23
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Human immunodeficiency virus type 1 g p m C5 region mimics the HLA class I a1 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 p-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 a1 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. O n 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.
* This work was supported by grants of Minister0 della Saniti