Cytomegalovirus (CMV) IE1- and pp65-specific CD8+ T cell responses broaden over time after primary CMV infection in infants

J Infect Dis. 2007 Jun 15;195(12):1789-98. doi: 10.1086/518042. Epub 2007 May 8.

Abstract

Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality in young children. We have previously shown that CD8+ T cell responses to CMV pp65 or IE1 protein were readily detectable in children with congenital or postnatal CMV infection. Here, we have further characterized the evolution of the peptide specificity of these responses in 7 infants<6 months of age at the start of the study. Thirteen pp65 and 15 IE1 peptides (median, 5 peptides/infant) were targeted, and most (61%) represented sequences not previously reported. Peptide specificity remained stable or broadened over time despite the clearance of CMV viremia. Loss of peptide recognition was not observed. Responses with the highest functional peptide avidity were not necessarily detected earliest. These data provide additional evidence that young infants can generate diverse CMV-specific CD8+ T cell responses but show that early responses may exhibit relatively focused peptide specificity and lower peptide avidity.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Antigens, Viral / immunology
  • Antigens, Viral / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cohort Studies
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / blood
  • Cytomegalovirus Infections / congenital
  • Cytomegalovirus Infections / immunology*
  • Humans
  • Immediate-Early Proteins / immunology*
  • Immediate-Early Proteins / metabolism
  • Infant
  • Leukocytes, Mononuclear / immunology
  • Peptide Mapping
  • Phosphoproteins / immunology*
  • Phosphoproteins / metabolism
  • Time Factors
  • Viral Load
  • Viral Matrix Proteins / immunology*
  • Viral Matrix Proteins / metabolism
  • Viral Proteins / immunology*
  • Viral Proteins / metabolism

Substances

  • Antigens, Viral
  • IE1 protein, cytomegalovirus
  • Immediate-Early Proteins
  • Phosphoproteins
  • Viral Matrix Proteins
  • Viral Proteins
  • cytomegalovirus matrix protein 65kDa