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.