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

BackgroundThe 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.MethodsTo 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.ResultsIn 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.ConclusionsThis 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.

Downregulation of CD5 and dysregulated CD8+ T‐cell activation

“…The cells were non‐activated, naive lymphocytes and had an impaired ability to proliferate in response to mitogenic and antigenic stimuli. A recent study suggested that downregulation of CD5 on HIV‐specific CD8 + T cells might represent in vivo adaptation to HIV variant peptides . In addition to these immune responses, malignant transformation may affect antigen expression on T cells.…”

“…A recent study suggested that downregulation of CD5 on HIV-specific CD8 + T cells might represent in vivo adaptation to HIV variant peptides. 23 In addition to these immune responses, malignant transformation may affect antigen expression on T cells. It is well known that loss or low expression of CD5 occurs in subgroups of patients with peripheral or precursor T-cell neoplasms.…”

Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents

“…These findings position sCD5 as a feasible therapeutic agent provided that sCD5-HCV interaction interferes with binding of HCV to other receptors known to be involved in hepatocyte entry [56]. Besides CD5 and HCV interaction, the possibility that sCD5 could have a role in modulating other viral infections exists as CD5 adapts its surface expression in lymphocyte subsets during Hepatitis B virus [57], HIV-1 [58], Equine Infectious Anemia [59] and Epstein-Barr Virus-associated hemophagocytic lymphohistiocytosis [60] infections.…”

Enhancing Human Immunodeficiency Virus-Specific CD8+ T Cell Responses with Heteroclitic Peptides

“…A threefold increase in levels of the HLA-A*0201-peptide complex on the surface of antigen-presenting cells (APC) pulsed with the heteroclitic variants was thought to underlie the enhanced CTL responses (43,44). Another study suggested that HIV protease (PR) peptide 76-84 (LVGPTPVNI), acting as a heteroclitic variant of IFN-γ-inducible protein 30 (IP-30) signal peptide −11 to −3 (LLDVPTAAV), activates autoreactive T cells in a subset of HIV-1-infected individuals expressing HLA-A2 (45,46). Therefore, exposure to heteroclitic peptides can potentially cut both ways with promotion of autoimmunity through the activation of self-reactive T cells an equally possible outcome as enhancement of T cell responses against foreign or tumor antigens.…”