Antagonism of HIV-specific CD4+ T cells by C-terminal truncation of a minimum epitope.
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.
Norris
Philip J
PJ
Blood Systems Research Institute, Department of Laboratory Medicine, University of California, 270 Masonic Avenue, San Francisco, CA 94118, USA. pnorris@bloodsystems.org
Stone
Jennifer D
JD
Anikeeva
Nadezhda
N
Heitman
John W
JW
Wilson
Ingrid C
IC
Hirschkorn
Dale F
DF
Clark
Margaret J
MJ
Moffett
Howell F
HF
Cameron
Thomas O
TO
Sykulev
Yuri
Y
Stern
Lawrence J
LJ
Walker
Bruce D
BD
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D016655:HIV Core Protein p24 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008213:Lymphocyte Activation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
D000939:Epitopes; D016655:HIV Core Protein p24; D015798:HLA-DR1 Antigen; D008024:Ligands; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell