       Document 0148
 DOCN  M95B0148
 TI    Identification of HIV protein-derived cytotoxic T lymphocyte (CTL)
       epitopes for their possible use as synthetic vaccine.
 DT    9511
 AU    Brander C; Pichler WJ; Corradin G; Institute of Immunology and
       Allergology, Inselspital, Bern,; Switzerland.
 SO    Clin Exp Immunol. 1995 Jul;101(1):107-13. Unique Identifier : AIDSLINE
       MED/95347061
 AB    CTL are by far the most important defence mechanisms against viral
       infections, and many attempts have been undertaken to induce protective
       CTL in vivo. In order to identify CTL epitopes for their possible use as
       peptide-vaccine candidates, HIV proteins were screened for peptide
       sequences which (i) fulfil the binding motif of the HLA-A2.1 molecule,
       and (ii) are involved in the natural immune response to HIV. From 73
       nonameric peptides satisfying the binding motif, 20 peptides were
       synthesized and their binding to HLA-A2.1 was monitored by measuring the
       expression of HLA-A2.1 molecules on the cell surface of the mutant cell
       line T2. To evaluate the involvement in natural HIV infection, strongly
       binding peptides were used in cytotoxicity assays to assess their
       capacity to generate a peptide-specific CTL response in vitro. From 20
       nonameric peptides synthesized, only five showed strong binding to
       HLA-A2.1. All five binding peptides had the secondary anchor residues,
       recently proposed by Ruppert et al. [1] to be required for binding to
       HLA-A2.1. The discrimination between bound and unbound peptides
       confirmed the importance of these secondary anchor residues which,
       beside the known binding motif, may dictate if a peptide can bind to
       HLA-A2.1 or not. In HIV- donors, no CTL activity against any of the
       HIV-derived peptides was detectable after a 12-day in vitro stimulation.
       In contrast, HIV-infected persons showed a cytotoxic response against
       peptide-labelled target cells, suggesting that they had developed upon
       HIV infection a cytotoxic immune response against the identified CTL
       epitopes.
 DE    Amino Acid Sequence  Cell Line  Epitope Mapping/*STANDARDS  Human  HIV
       Antigens/*IMMUNOLOGY/*METABOLISM  HLA-A2 Antigen/GENETICS/*METABOLISM
       Molecular Sequence Data  Protein Binding/PHYSIOLOGY  Support, Non-U.S.
       Gov't  T-Lymphocytes, Cytotoxic/*IMMUNOLOGY  Vaccines,
       Synthetic/BIOSYNTHESIS  JOURNAL ARTICLE

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

