T cell multideterminant regions in the human immunodeficiency virus envelope: Toward overcoming the problem of major histocompatibility complex restriction

P. M. Hale, K. B. Cease, R. A. Houghten, C. Ouyang, S. Putney, K. Javaherian, H. Margalit, J. L. Cornette, J. L. Spouge, C. Delisi, J. A. Berzofsky1*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Helper T cell determinants should be an Important component of an anti-human Immunodeficiency virus (HIV) vaccine aimed at either antibody or cytotoxic T cell Immunity. However, model protein studies have raised concern about the usefulness of any single determinant, because a given determinant is likely to be seen by only a small subset of major histocompatibility complex (MHC) types within the population. Here, we use 44 peptides, including ones predicted and not predicted on the basis of amphipathicity to be potential T cell sites, to locate T cell antigenic determinants recognized by mice of four MHC haplotypes immunized with the whole gp160 envelope protein. Although the preselection of peptides necessitates caution In a statistical analysis, α-amphipathic peptides predominated among sites eliciting the strongest response. Although we have not tested the entire sequence, we have identified six multldetermlnant regions, in which overlapping peptides are recognized by mice of either three or all four MHC types. Four of the six regions have sequences relatively conserved among HIV-1 isolates. The existence of such multideterminant regions recognized by multiple MHC haplotypes suggests the possibility that use of peptides longer than a minimal determinant and containing several overlapping determinants may be a possible approach to circumvent the serious problem of MHC restriction in peptide vaccines aimed at eliciting T cell immunity.

Original languageAmerican English
Pages (from-to)409-415
Number of pages7
JournalInternational Immunology
Volume1
Issue number4
DOIs
StatePublished - Sep 1989
Externally publishedYes

Bibliographical note

Funding Information:
1Metabolism Branch and5Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA department of Molecular Biology, Scnpps Clinic and Research Foundation, La Jolla, CA 92037, USA 4Repligen Corporation, Cambridge, MA 02139, USA 'Department of Biomathematical Sciences, Mount Sinai Medical School, New York, NY 10029, USA

Keywords

  • AIDS
  • Amphipathicity
  • Peptides
  • T cell epitopes
  • Vaccines

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