18 results found
Yang H, Rei M, Brackenridge S, et al., 2021, HLA-E-restricted, Gag-specific CD8(+) T cells can suppress HIV-1 infection, offering vaccine opportunities, Science Immunology, Vol: 6, Pages: 1-11, ISSN: 2470-9468
Human leukocyte antigen-E (HLA-E) normally presents an HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (SIV) vaccine generated Mamu-E (HLA-E homolog)–restricted T cell responses that mediated post-challenge SIV replication arrest in >50% of animals. However, HIV-1–specific, HLA-E–restricted T cells have not been observed in HIV-1–infected individuals. Here, HLA-E–restricted, HIV-1–specific CD8+ T cells were primed in vitro. These T cell clones and allogeneic CD8+ T cells transduced with their T cell receptors suppressed HIV-1 replication in CD4+ T cells in vitro. Vaccine induction of efficacious HLA-E–restricted HIV-1–specific T cells should therefore be possible.
Peng BJ, Carlson JM, Liu MKP, et al., 2018, Antisense-Derived HIV-1 Cryptic Epitopes Are Not Major Drivers of Viral Evolution during the Acute Phase of Infection, JOURNAL OF VIROLOGY, Vol: 92, ISSN: 0022-538X
Liu D, Wang C, Hora B, et al., 2017, A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies, Retrovirology, Vol: 14, ISSN: 1742-4690
Background: Mutations rapidly accumulate in the HIV-1 genome after infection. Some of those mutations areselected by host immune responses and often cause viral ftness losses. This study is to investigate whether stronglyselected mutations that are not associated with immune responses result in ftness losses.Results: Strongly selected mutations were identifed by analyzing 5′-half HIV-1 genome (gag/pol) sequences fromlongitudinal samples of subject CH0131. The K43R mutation in the gag gene was frst detected at day 91 post screeningand was fxed in the viral population at day 273 while the synonymous N323tc mutation was frst detected at day177 and fxed at day 670. No conventional or cryptic T cell responses were detected against either mutation sites byELISpot analysis. However, when ftness costs of both mutations were measured by introducing each mutation intotheir cognate transmitted/founder (T/F) viral genome, the K43R mutation caused a signifcant ftness loss while theN323tc mutation had little impact on viral ftness.Conclusions: The rapid fxation, the lack of detectable immune responses and the signifcant ftness cost of theK43R mutation suggests that it was strongly selected by host factors other than T cell responses and neutralizingantibodies
Song H, Hora B, Bhattacharya T, et al., 2014, Reversion and T Cell Escape Mutations Compensate the Fitness Loss of a CD8(+) T Cell Escape Mutant in Their Cognate Transmitted/Founder Virus, PLOS ONE, Vol: 9, ISSN: 1932-6203
Liu MKP, Hawkins N, Ritchie AJ, et al., 2013, Vertical T cell immunodominance and epitope entropy determine HIV-1 escape, JOURNAL OF CLINICAL INVESTIGATION, Vol: 123, Pages: 380-393, ISSN: 0021-9738
Song H, Pavlicek JW, Cai F, et al., 2012, Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome., Retrovirology, Vol: 9
BACKGROUND: A modest change in HIV-1 fitness can have a significant impact on viral quasispecies evolution and viral pathogenesis, transmission and disease progression. To determine the impact of immune escape mutations selected by cytotoxic T lymphocytes (CTL) on viral fitness in the context of the cognate transmitted/founder (T/F) genome, we developed a new competitive fitness assay using molecular clones of T/F genomes lacking exogenous genetic markers and a highly sensitive and precise parallel allele-specific sequencing (PASS) method. RESULTS: The T/F and mutant viruses were competed in CD4+ T-cell enriched cultures, relative proportions of viruses were assayed after repeated cell-free passage, and fitness costs were estimated by mathematical modeling. Naturally occurring HLA B57-restricted mutations involving the TW10 epitope in Gag and two epitopes in Tat/Rev and Env were assessed independently and together. Compensatory mutations which restored viral replication fitness were also assessed. A principal TW10 escape mutation, T242N, led to a 42% reduction in replication fitness but V247I and G248A mutations in the same epitope restored fitness to wild-type levels. No fitness difference was observed between the T/F and a naturally selected variant carrying the early CTL escape mutation (R355K) in Env and a reversion mutation in the Tat/Rev overlapping region. CONCLUSIONS: These findings reveal a broad spectrum of fitness costs to CTL escape mutations in T/F viral genomes, similar to recent findings reported for neutralizing antibody escape mutations, and highlight the extraordinary plasticity and adaptive potential of the HIV-1 genome. Analysis of T/F genomes and their evolved progeny is a powerful approach for assessing the impact of composite mutational events on viral fitness.
Riou C, Treurnicht F, Abrahams M-R, et al., 2012, Increased Memory Differentiation Is Associated with Decreased Polyfunctionality for HIV but Not for Cytomegalovirus-Specific CD8(+) T Cells, JOURNAL OF IMMUNOLOGY, Vol: 189, Pages: 3838-3847, ISSN: 0022-1767
Riou C, Ganusov VV, Campion S, et al., 2012, Distinct Kinetics of Gag-Specific CD4(+) and CD8(+) T Cell Responses during Acute HIV-1 Infection, JOURNAL OF IMMUNOLOGY, Vol: 188, Pages: 2198-2206, ISSN: 0022-1767
Ganusov VV, Goonetilleke N, Liu MKP, et al., 2011, Fitness Costs and Diversity of the Cytotoxic T Lymphocyte (CTL) Response Determine the Rate of CTL Escape during Acute and Chronic Phases of HIV Infection, JOURNAL OF VIROLOGY, Vol: 85, Pages: 10518-10528, ISSN: 0022-538X
Brackenridge S, Evans EJ, Toebes M, et al., 2011, An Early HIV Mutation within an HLA-B*57-Restricted T Cell Epitope Abrogates Binding to the Killer Inhibitory Receptor 3DL1, JOURNAL OF VIROLOGY, Vol: 85, Pages: 5415-5422, ISSN: 0022-538X
Ritchie AJ, Campion SL, Kopycinski J, et al., 2011, Differences in HIV-Specific T Cell Responses between HIV-Exposed and -Unexposed HIV-Seronegative Individuals, JOURNAL OF VIROLOGY, Vol: 85, Pages: 3507-3516, ISSN: 0022-538X
Ferrari G, Korber B, Goonetilleke N, et al., 2011, Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection, PLOS PATHOGENS, Vol: 7, ISSN: 1553-7366
Kramer HB, Lavender KJ, Qin L, et al., 2010, Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection, PLOS PATHOGENS, Vol: 6, ISSN: 1553-7366
Goonetilleke N, Liu MKP, Salazar-Gonzalez JF, et al., 2009, The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection, JOURNAL OF EXPERIMENTAL MEDICINE, Vol: 206, Pages: 1253-1272, ISSN: 0022-1007
MacLennan CA, Liu MKP, White SA, et al., 2007, Diagnostic accuracy and clinical utility of a simplified low cos method of counting CD4 cells with flow cytometry in Malawi diagnostic accuracy study, BRITISH MEDICAL JOURNAL, Vol: 335, Pages: 190-194, ISSN: 0959-8146
Sweenie CH, Mackenzie KJ, Rone-Orugboh A, et al., 2007, Distinct T cell recognition of naturally processed and cryptic epitopes within the immunodominant 35–55 region of myelin oligodendrocyte glycoprotein, Journal of Neuroimmunology, Vol: 183, Pages: 7-16, ISSN: 0165-5728
Manzotti CN, Liu MKP, Burke F, et al., 2006, Integration of CD28 and CTLA-4 function results in differential responses of T cells to CD80 and CD86., Eur J Immunol, Vol: 36, Pages: 1413-1422, ISSN: 0014-2980
CD80 and CD86 have the capacity to either stimulate or inhibit T cell responses through their receptors CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Blockade of CD80 and CD86 in autoimmune disease settings has revealed distinct outcomes, yet the differential functions of CD80 and CD86 are still unclear. We have studied the ability of individual ligands to stimulate primary responses in human CD4(+) T cells. Our data reveal both quantitative and qualitative differences between the ligands. Both CD80 and CD86 demonstrated the capacity to costimulate T cell proliferation. However, CD80 committed a greater number of T cells to divide with faster kinetics, consistent with it being a superior ligand for CD28. Once cell division had been initiated, all T cells undergoing cell division expressed CTLA-4, irrespective of whether CD80 or CD86 costimulation was used. However, only in the presence of CD80 was evidence of CTLA-4 engagement and inhibitory function observed. Finally, differences between CD80 and CD86 costimulation extended to the T cell phenotype, in particular the levels of CD40 ligand expression.
Mead KI, Zheng Y, Manzotti CN, et al., 2005, Exocytosis of CTLA-4 is dependent on phospholipase D and ADP ribosylation factor-1 and stimulated during activation of regulatory T cells, JOURNAL OF IMMUNOLOGY, Vol: 174, Pages: 4803-4811, ISSN: 0022-1767
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