Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses

• Published in: PloS one Vol. 13; no. 2; p. e0192098
• Main Authors: Pohlmeyer, Christopher W., Laskey, Sarah B., Beck, Sarah E., Xu, Daniel C., Capoferri, Adam A., Garliss, Caroline C., May, Megan E., Livingston, Alison, Lichmira, Walt, Moore, Richard D., Leffell, M. Sue, Butler, Nicholas J., Thorne, Jennifer E., Flynn, John A., Siliciano, Robert F., Blankson, Joel N.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.02.2018; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adaptive immunity; AIDS; Antigens; Biology and Life Sciences; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cross Reactions; Cytotoxicity; Epitopes; HIV; HIV Infections - immunology; HIV-1 - drug effects; HIV-1 - immunology; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immune response; Immune system; Immunity; Immunodominance; Infections; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Medicine; Medicine and Health Sciences; Microorganisms; Mutation; Peptides; Peripheral blood mononuclear cells; Research and Analysis Methods; Stimulation; T cell receptors; T-cell receptor; Virus Replication - drug effects; California; United States > US; Maryland; Baltimore Maryland; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0192098

Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects. Despite these differences, CD8+ T cells stimulated with either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication in autologous CD4+ T cells. These data suggest that exposure to cross-reactive microbial antigens can modulate HIV-1-specific immunity.