title: Greater frequency of CD5-negative CD8(+) T cells against human immunodeficiency virus type 1 than other viruses is consistent with adaptation to antigenic variation.
abstract: BACKGROUND
  The CD5 protein antagonizes phosphorylation events downstream of T cell receptor (TCR) engagement to decrease T cell responsiveness. CD5-negative T cell clones respond preferentially over their CD5(+) counterparts against cells with low human histocompatibility-linked leukocyte antigen (HLA) levels. In human immunodeficiency virus type 1 (HIV-1) infection, CD5(-)CD8(+) T cells increase in prevalence with disease progression.
  
  
  METHODS
  To investigate potential causes of this expansion of CD5(-)CD8(+) T cells in HIV-1 infection, we compared CD5 expression on CD8(+) T cells reactive against HIV-1 peptides, common viral peptides and a self peptide that together span a broad range of TCR avidities in the context of the common HLA-A2 class I restriction molecule. Following stimulation, CD5 expression on peptide-specific CD8(+) T cells was assessed by flow cytometry.
  
  
  RESULTS
  In healthy controls, there was no significant difference in the CD5(+) percentage of CD8(+) T cells specific for common viral peptides, but a lower percentage of those responding against a common self peptide expressed CD5. The same relationship occurred in HIV-infected individuals, however, a lower percentage of HIV peptide-specific CD8(+) T cells than other viral peptide-specific CD8(+) T cells expressed CD5. In terms of overall CD5 expression level at the peptide-specific responder population level, HIV-specific CD8(+) T cells resembled those responsive against the self peptide, despite much higher avidity TCR/HLA/peptide interactions.
  
  
  CONCLUSIONS
  This deficit in CD5 expression selective for HIV-specific CD8(+) T cells is consistent with in vivo adaptation to low avidity HIV peptide variants and has potential consequences for CD8(+) T cell expansion, cross-reactivity and autoreactivity.
authors.affiliation: Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3 V6, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Penney
authors.affiliation: Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3 V6, Canada.
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Gallant
authors.affiliation: Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3 V6, Canada ; H1803-Immunology, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, NL A1B 3 V6, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Grant
keywords: Avidity; CD5; CD8+ T cell; HIV; HLA class I; Peptide; T cell receptor