       Document 0076
 DOCN  M9640076
 TI    Class I-restricted presentation of an HIV-1 gp41 epitope containing an
       N-linked glycosylation site. Implications for the mechanism of
       processing of viral envelope proteins.
 DT    9604
 AU    Ferris RL; Buck C; Hammond SA; Woods AS; Cotter RJ; Takiguchi M;
       Igarashi Y; Ichikawa Y; Siliciano RF; Department of Medicine, Johns
       Hopkins University School of; Medicine, Baltimore, MD 21205, USA.
 SO    J Immunol. 1996 Jan 15;156(2):834-40. Unique Identifier : AIDSLINE
       MED/96133015
 AB    Uncertainty exists over the site of processing of viral envelope (env)
       proteins for recognition by CTL. The extracellular domains of env
       proteins are not present in the cytosol, the site where the class I Ag
       processing pathway begins. Rather, the ecto-domains of env proteins are
       cotranslationally translocated into the endoplasmic reticulum during
       biosynthesis. To clarify the site of processing of viral env proteins,
       we examined the processing of an HLA B*3501-restricted epitope in the
       extracellular domain of the HIV-1 env protein. Although this epitope
       contains an N-linked glycosylation signal sequence, CTL specific for
       this epitope recognize a nonameric peptide that has not been previously
       modified by attachment of oligosaccharide. This was demonstrated in two
       ways. First, an env-specific B*3501-restricted CTL clone recognized a
       nonglycosylated, synthetic nonamer representing the minimal
       B*3501-restricted epitope, but not the glycosylated or deglycosylated
       forms. Second, the naturally processed, B*3501-restricted, env peptide
       is identical with a nonglycosylated, synthetic nonamer. Thus, the
       naturally processed form of an env epitope containing an N-linked
       glycosylation site is derived from env protein that is not glycosylated
       at the relevant asparagine during biosynthesis. Since the addition of
       N-linked oligosaccharides occurs only after the glycosylation signal
       sequence (N-X-S/T) is translocated into the endoplasmic reticulum, the
       initial processing reaction for this epitope may take place in the
       cytosol. Low-frequency failure of signal sequence containing
       polypeptides to engage the translocation apparatus, resulting in
       synthesis and degradation in the cytosol, may represent an important
       mechanism for the generation of class I-restricted CTL responses.
 DE    *Antigen Presentation  Epitopes/CHEMISTRY/*IMMUNOLOGY  Glycosylation
       Human  HIV Envelope Protein gp41/CHEMISTRY/*IMMUNOLOGY/METABOLISM
       HIV-1/*IMMUNOLOGY  HLA-B Antigens/*IMMUNOLOGY  Macromolecular Systems
       Peptide Fragments/IMMUNOLOGY/METABOLISM  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  T-Lymphocytes, Cytotoxic/*IMMUNOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

