Document 0355
 DOCN  M9650355
 TI    N-linked glycans in the CD4-binding domain of human immunodeficiency
       virus type 1 envelope glycoprotein gp160 are essential for the in vivo
       priming of T cells recognizing an epitope located in their vicinity.
 DT    9605
 AU    Sjolander S; Bolmstedt A; Akerblom L; Horal P; Olofsson S; Morein B;
       Sjolander A; Department of Veterinary Microbiology, College of
       Veterinary; Medicine, Swedish University of Agricultural Sciences,
       Uppsala,; Sweden.
 SO    Virology. 1996 Jan 15;215(2):124-33. Unique Identifier : AIDSLINE
       MED/96146726
 AB    Deglycosylation of viral glycoproteins has been suggested to influence
       the number of available T cell determinants and to increase T cell
       recognition of antigens. In this study, we have investigated whether T
       cell responses to the HIV-1 envelope glycoprotein gp160 were influenced
       by deletion of three N-glycans of the protein. Wild type (wt) and a
       mutated form of gp160 (gp160A123) lacking the three N-glycans in the
       C-terminal CD4-binding region efficiently induced antigen-specific T
       cell responses in mice of the H-2b, H-2d, and H-2k haplotypes. Further,
       T cells primed by either wt gp160 or gp160A123 were stimulated in vitro
       to a similar extent by the homologous and heterologous protein,
       indicating that deletion of the glycans did not affect the overall
       immunogenicity and antigenicity of gp160A123. Wild-type gp160 and
       gp160A123 induced comparable T cell responses to those of epitopes which
       with respect to the secondary structure of gp160 were distant from the
       deleted glycans. However, in mice of the H-2b haplotype, wt gp160 primed
       T cells which responded in vitro to a peptide containing one of the
       deleted N-glycosylation sites (Asn448), whereas T cells induced by
       gp160A123 were unable to recognize this peptide. Thus, deletion of the
       glycans abrogated the in vivo priming of T cells recognizing an epitope
       in close proximity to the deletion sites. Furthermore, enzymatically
       deglycosylated gp160 failed to induce a T cell response to this epitope.
       These results indicate that the in vivo generation of certain T cell
       determinants from glycoproteins is dependent on the glycosylation of the
       protein.
 DE    Amino Acid Sequence  Animal  Antigens, CD4/METABOLISM
       Asparagine/IMMUNOLOGY  CD4-Positive T-Lymphocytes/*IMMUNOLOGY
       Epitopes/IMMUNOLOGY  Female  Gene Products, env/*IMMUNOLOGY
       Glycosylation  Human  HIV-1/*IMMUNOLOGY  Mice  Mice, Inbred BALB C
       Mice, Inbred CBA  Mice, Inbred C57BL  Molecular Sequence Data
       Polysaccharides/*IMMUNOLOGY/METABOLISM  Protein Precursors/*IMMUNOLOGY
       Species Specificity  Structure-Activity Relationship  Support, Non-U.S.
       Gov't  JOURNAL ARTICLE

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