       Document 0077
 DOCN  M9440077
 TI    Epitope selection and design of synthetic vaccines (Meeting abstract).
 DT    9404
 AU    Berzofsky JA; NCI, Bethesda, MD 20892
 SO    Specific Immunotherapy of Cancer with Vaccines. January 21-24, 1993,
       Washington, DC, A30 1993.. Unique Identifier : AIDSLINE ICDB/94698148
 AB    Recent advances in the understanding of antigen processing and
       presentation facilitate the identification of antigenic sites recognized
       by CD4+ helper T cells and by CD8+ cytotoxic T lymphocytes (CTL), and
       suggest methods to optimize the activity of these for construction of
       synthetic peptide vaccines aimed at eliciting T-cell immunity. We have
       characterized the functional role of each residue in an HIV envelope
       peptide recognized by helper T cells from mice and humans. Only a few of
       the amino acid residues were necessary for binding to class II MHC
       molecules and immunogenicity. The other residues were more remarkable
       for the negative impact they could have. A more potent peptide antigen
       was produced by replacing one of these with Ala, emphasizing the
       importance of adverse interactions in peptide-MHC binding. Similarly for
       an HIV-1 CTL site presented by multiple murine and human class I MHC
       molecules, CTL specificity was shown to focus on the distinction between
       aromatic and aliphatic side chains at one position. This in turn allowed
       the construction of chimeric peptides that induced broadly
       cross-reactive CTL responses. We have also addressed the problem of MHC
       polymorphism by using multideterminant regions spanning overlapping
       sites presented by different MHC molecules, and by identifying
       promiscuously presented peptides. Thus, understanding the molecular
       basis for T-cell recognition can facilitate improvements in synthetic
       vaccines beyond the natural sequences. Similar approaches can be applied
       to tumor antigens.
 DE    Animal  Antigenic Determinants/*GENETICS/IMMUNOLOGY  Drug Design  Human
       *Immunotherapy  Major Histocompatibility Complex/GENETICS/IMMUNOLOGY
       Melanoma/IMMUNOLOGY/THERAPY  Mice  Polymorphism (Genetics)
       T-Lymphocytes, Cytotoxic/*IMMUNOLOGY  T-Lymphocytes,
       Helper-Inducer/IMMUNOLOGY  *Vaccines, Synthetic  Viral Envelope
       Proteins/IMMUNOLOGY  MEETING ABSTRACT

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

