Epitope selection and design of synthetic vaccines (Meeting abstract).

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Epitope selection and design of synthetic vaccines (Meeting abstract).

Specific Immunotherapy of Cancer with Vaccines. January 21-24, 1993, Washington, DC, A30 1993.. Unique Identifier : AIDSLINE ICDB/94698148
Berzofsky JA; NCI, Bethesda, MD 20892

Abstract: 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.

Keywords: Animal Drug Design Epitopes/*GENETICS/IMMUNOLOGY 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 ABSTRACT
940530
M9450892

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