Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Yaciuk, Jane C.; Skaley, Matthew; Bardet, Wilfried; Schafer, Fredda; Mojsilovic, Danijela; Cate, Steven; Stewart, Christopher; McMurtrey, Curtis P.; Jackson, Kenneth W.; Buchli, Rico; Olvera, Àlex; Cedeño, Samandhy; Plana, Montserrat; Mothe, Beatriz; Berthou, Christian; West, John T.; Hildebrand, William H.

doi:10.1128/jvi.01914-14

Cited by 44 publications

(60 citation statements)

References 36 publications

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“…While 293T cells and CD4 T cells share HLA-A02, the three cell types covered a diversity of HLAs reflective of the HLA diversity of the population. Despite this diversity, the majority of peptides were derived from Gag, which reflects the larger amount of Gag present both in incoming virions and in neosynthesized particles and is in accordance with the distribution of HIV peptides reported in other studies (9,17). The second-most-abundant protein presented by all three cell types was Pol, whereas Nef and Env were the proteins that were the second most sampled by soluble HLA-A11 in reference 9 and by CD4 T cells in reference 17, respectively.…”

Section: Discussionsupporting

confidence: 74%

“…Most (64% to 80%) HIV peptides were 8 to 12 aa long, but 17% to 31% of the longer (13-to-18-aa) noncanonical peptides were also identified in all three cell types. The distributions are in accordance with the size distributions of HIV peptides isolated from HIV-infected T cell lines (9,17) and were similar for HIV-derived and self-derived peptides. However, the total number of self-peptides (601 to 1,184) was expectedly higher as observed in HIV and other viral infections (5,9,17,29).…”

Section: Methodssupporting

confidence: 68%

“…The distributions are in accordance with the size distributions of HIV peptides isolated from HIV-infected T cell lines (9,17) and were similar for HIV-derived and self-derived peptides. However, the total number of self-peptides (601 to 1,184) was expectedly higher as observed in HIV and other viral infections (5,9,17,29). In all three cell types, the majority of HIV peptides were derived from structural proteins Gag and Pol, although in differing proportions (Fig.…”

Section: Methodssupporting

confidence: 68%

“…This MHC-peptidome study and others in viral infections (9,15,16) or in B cell lines (30,(42)(43)(44)(45) identified clusters of nested peptides. They include optimal epitopes as well as N-and/or Cextended peptides potentially presentable by several HLAs.…”

Section: Discussionmentioning

confidence: 99%

“…However, considering the relatively low number of MHC-peptide complexes per cell and the potential MS detection limits, the majority of the data on self-, cancer, or pathogen MHC peptidomes come from immortalized cell lines (5)(6)(7)(8) or from models using cell lines engineered to secrete soluble MHC-bound peptide complexes (9)(10)(11), as both systems allow growth of high numbers of cells for peptide isolation. The improvements in peptide isolation and MS-based approaches led to the discovery of numerous MHC-I ligands presented by B cells or by patients' tumors (12)(13)(14) and the identification of virusderived MHC-bound peptides, including vaccinia virus and HIV presented by surface or soluble HLA (5,9,(15)(16)(17). These approaches identified self-and virus-derived noncanonical peptides and demonstrated that direct identification of peptides from infected cells will define the immunopeptidome relevant for the design of HIV immunogens.…”

mentioning

confidence: 99%

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Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses

Ručević

Kourjian

Boucau

et al. 2016

J Virol

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H IV-specific T cells play an important role in the containment of infection as evidenced by the concurrent drop of viral load and the appearance of HIV-specific CD8 T cells in acute infection, T cell-driven immune pressure leading to predictable HLA-restricted HIV mutations, and the association between specific HLAs and epitopes or immune responses to specific proteins and spontaneous control of HIV. However, the lack of clear correlates of immune protection hampers efficient vaccine design (1).Screening and functional studies of T cells from HIV-infected persons or vaccinees use high nonphysiological concentrations of long HIV peptides exogenously pulsed onto cells or soluble major histocompatibility complex (MHC)-peptide multimers presenting peptides of optimal size (2, 3). These approaches bypass all steps required for intracellular antigen processing and presentation of HIV peptides by MHC class I (MHC-I) molecules (4). Determination of the amounts and sequences of peptides presented by an infected cell remains largely elusive despite the role of the peptides in immune recognition.Direct mass spectrometry (MS)-based sequencing has become a preferred and yet difficult approach for the unbiased identification and characterization of peptides naturally presented by MHC-I molecules displayed by healthy and cancerous cells or in the context of pathogen infection. However, considering the relatively low number of MHC-peptide complexes per cell and the

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Section: Discussionsupporting

confidence: 74%

Section: Methodssupporting

confidence: 68%

Section: Methodssupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses

Ručević

Kourjian

Boucau

et al. 2016

J Virol

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Defining the HLA class I‐associated viral antigen repertoire from HIV‐1‐infected human cells

et al. 2015

Self Cite

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Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High‐throughput definition of HLA class I‐associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding of the induction of T‐cell responses against pathogens such as HIV‐1. We utilized a liquid chromatography tandem mass spectrometry workflow including de novo‐assisted database searching to define the HLA class I‐associated immunopeptidome of HIV‐1‐infected human cells. We here report for the first time the identification of 75 HIV‐1‐derived peptides bound to HLA class I complexes that were purified directly from HIV‐1‐infected human primary CD4+ T cells and the C8166 human T‐cell line. Importantly, one‐third of eluted HIV‐1 peptides had not been previously known to be presented by HLA class I. Over 82% of the identified sequences originated from viral protein regions for which T‐cell responses have previously been reported but for which the precise HLA class I‐binding sequences have not yet been defined. These results validate and expand the current knowledge of virus‐specific antigenic peptide presentation during HIV‐1 infection and provide novel targets for T‐cell vaccine development.

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Mass Spectrometry in Virological Sciences

Milewska

Ner‐Kluza

Dąbrowska

et al. 2019

Mass Spectrometry Reviews

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Virology, as a branch of the life sciences, discovered mass spectrometry (MS) to be the pivotal tool around two decades ago. The technique unveiled the complex network of interactions between the living world of pro-and eukaryotes and viruses, which delivered "a piece of bad news wrapped in protein" as defined by Peter Medawar, Nobel Prize Laureate, in 1960. However, MS is constantly evolving, and novel approaches allow for a better understanding of interactions in this micro-and nanoworld. Currently, we can investigate the interplay between the virus and the cell by analyzing proteomes, interactomes, virus-cell interactions, and search for the compounds that build viral structures. In addition, by using MS, it is possible to look at the cell from the broader perspective and determine the role of viral infection on the scale of the organism, for example, monitoring the crosstalk between infected tissues and the immune system. In such a way, MS became one of the major tools for the modern virology, allowing us to see the infection in the context of the whole cell or the organism.

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Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Abstract: Identification of CD8

Cited by 44 publications

References 36 publications

Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses

Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses

Defining the HLA class I‐associated viral antigen repertoire from HIV‐1‐infected human cells

Mass Spectrometry in Virological Sciences

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