Conservation of cytotoxic T lymphocyte (CTL) epitopes as a host strategy to constrain parasite adaptation: evidence from the nef gene of human immunodeficiency virus 1 (HIV-1)

Mol Biol Evol. 1998 Oct;15(10):1259-68. doi: 10.1093/oxfordjournals.molbev.a025854.


Host cytotoxic T lymphocytes (CTLs) that recognize specific viral peptides (epitopes) are thought to provide the most effective control of viral replication and spread. However, viruses may escape this recognition through mutations in CTL epitopes. We tested the hypothesis that, as an adaptation on the part of the host to constrain parasite escape from immune control, class I major histocompatibility complex (MHC) molecules present peptides that are derived from conserved regions of foreign proteins to CTLs. We did this by estimating the relative conservation of CTL epitopes of the functionally important Nef protein of human immunodeficiency virus 1 (HIV-1) and relating this to the structure and function of the protein. In comparisons among sequences from several HIV-1 subtypes and both major groups, CTL epitopes had lower rates of nonsynonymous nucleotide substitution per site than did the remainder of the protein, indicating the relative conservation of these epitopes. In contrast, helper T-cell epitopes were as conserved as, and monoclonal antibody epitopes less conserved than, the remainder of the protein. The conservation of CTL epitopes is apparently due to their derivation from functionally important domains of Nef, since CTL epitopes coincide with these domains and these domains are conserved relative to the remainder of the protein, in contrast to secondary structural elements, which are not. Recent studies provide evidence of CTL selection on HIV-1 epitopes, but the variational range of viral escape mutants appears to be limited by functional constraints on the protein regions from which epitopes are derived. The presentation of conserved foreign peptides to CTLs by class I MHC molecules may be a general adaptation of vertebrate hosts to constrain the adaptation of their intracellular parasites.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Antigen Presentation
  • DNA, Viral / genetics
  • Epitopes / genetics*
  • Epitopes / immunology
  • Gene Products, nef / immunology*
  • Genes, nef*
  • HIV Infections / immunology
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • HLA Antigens / immunology
  • Host-Parasite Interactions / immunology*
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Phylogeny
  • Proviruses / genetics
  • Selection, Genetic
  • Sequence Alignment
  • Sequence Homology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • nef Gene Products, Human Immunodeficiency Virus


  • DNA, Viral
  • Epitopes
  • Gene Products, nef
  • HLA Antigens
  • Peptide Fragments
  • nef Gene Products, Human Immunodeficiency Virus