Antagonism of HIV-specific CD4+ T cells by C-terminal truncation of a minimum epitope

Mol Immunol. 2006 Mar;43(9):1349-57. doi: 10.1016/j.molimm.2005.09.004. Epub 2005 Oct 7.

Abstract

Antagonism of T cell responses by variants of the cognate peptide is a potential mechanism of viral escape from immune responses and may play a role in the ability of HIV to evade immune control. We show here a rarely described mechanism of antagonism by a peptide shorter than the minimum length epitope for an HIV p24-specific CD4+ T cell clone. The shorter antagonist peptide-MHC complex bound the T cell receptor (TCR), albeit with lower affinity than the full-length agonist peptide. Prior work showing the crystal structure of the peptide-MHC complex revealed a unique glycine hinge near the C-terminus of the agonist peptide, allowing the generation of full-length antagonist peptide lacking the hinge. These results confirm the dependence of productive TCR engagement on residues spilling out from the C-terminus of the MHC binding groove and show that partial engagement of the TCR with a truncated, low-affinity ligand can result in T cell antagonism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology*
  • Epitopes / chemistry
  • Epitopes / immunology
  • HIV Core Protein p24 / chemistry
  • HIV Core Protein p24 / genetics
  • HIV Core Protein p24 / immunology*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HLA-DR1 Antigen / chemistry
  • HLA-DR1 Antigen / metabolism
  • Humans
  • In Vitro Techniques
  • Ligands
  • Lymphocyte Activation
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / metabolism

Substances

  • Epitopes
  • HIV Core Protein p24
  • HLA-DR1 Antigen
  • Ligands
  • Multiprotein Complexes
  • Peptide Fragments
  • Receptors, Antigen, T-Cell