Molecular characterisation of the monocytic cell line THP‐1 demonstrates a discrepancy with the documented HLA type

Battle, Richard; Poole, Katherine; Haywood-Small, Sarah; Clark, Brendan; Woodroofe, Nicola

doi:10.1002/ijc.27661

Cited by 15 publications

(14 citation statements)

References 12 publications

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“…Downregulation of MHC-I by HIV differs across MHC-I allotypes, whereby, HLA-A allotypes are more susceptible than HLA-B allotypes (16). Since A549 and THP-1 cell lines express a diverse set of HLA-I alleles (A549: A * 25:01, A * 30:01, B * 18, B * 44:03, C * 12:03, C * 16:01, and THP-1: A * 02, B * 15, C * 03) (17, 18), we next assessed how different HLA-A, -B, and C allotypes are downregulated during influenza infection. To that end, we used a library of 14 C1R cell lines transduced with single different HLA-A (A * 01:01, A * 02:01, A * 03:01, A * 24:02) or HLA-B (B * 07:02, B * 08:01, B * 15:01, B * 18:01, B * 27:05, B * 35:01, B * 44:02, B * 44:03, B * 44:05, B * 57:01) alleles.…”

Section: Resultsmentioning

confidence: 99%

Downregulation of MHC Class I Expression by Influenza A and B Viruses

et al. 2019

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Manipulation of the MHC-I presentation pathway, and thus limiting MHC-I cell surface expression, is used by many viruses to evade immune recognition. In particular, downregulation of MHC-I molecules at the cell surface can reduce the ability of CD8 + T cells to recognize viral peptides presented by MHC-I molecules and thereby delay viral clearance by CD8 + T cells. To date, MHC-I downregulation by influenza viruses has not been reported. Given that influenza virus infections are a global health concern and that CD8 + T cells play an important role in promoting influenza virus clearance and recovery from influenza disease, we investigated whether influenza A and B viruses (IAV, IBV) downregulated MHC-I as a novel mechanism to evade cellular immunity. Here, we showed that infection of several cell types, including epithelial A549 cells, with a panel of IAV and IBV viruses downregulated the surface MHC-I expression on IAV/IBV-infected cells during the late stages of influenza virus infection in vitro . This observation was consistent across a panel of class I-reduced (C1R) cell lines expressing 14 different HLA-A or -B alleles and a panel of 721.221 cell lines expressing 11 HLA-C alleles. Interestingly, IBV infection caused more pronounced reduction in surface MHC-I expression compared to IAV. Importantly, the two viruses utilized two distinct mechanisms for MHC-I downregulation. Our data demonstrated that while IAV caused a global loss of MHC-I within influenza-infected cells, IBV infection resulted in the preferential loss of MHC-I molecules from the cell surface, consequent of delayed MHC-I trafficking to the cell surface, resulting from retaining MHC-I intracellularly during IBV infection. Overall, our study suggests that influenza viruses across both IAV and IBV subtypes have the potential to downregulate MHC-I surface expression levels. Our findings provide new insights into the host-pathogen interaction of influenza A and B viruses and inform the design of novel vaccine strategies against influenza viruses.

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Section: Resultsmentioning

confidence: 99%

Downregulation of MHC Class I Expression by Influenza A and B Viruses

et al. 2019

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“…HLA typing information was retrieved from the original publications. In one case (THP-1 cell lines), the typing is controversial [ 53 ]. In this work, we used the typing determined by the authors of the HLA peptidomics study where the data came from [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity

et al. 2017

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The precise identification of Human Leukocyte Antigen class I (HLA-I) binding motifs plays a central role in our ability to understand and predict (neo-)antigen presentation in infectious diseases and cancer. Here, by exploiting co-occurrence of HLA-I alleles across ten newly generated as well as forty public HLA peptidomics datasets comprising more than 115,000 unique peptides, we show that we can rapidly and accurately identify many HLA-I binding motifs and map them to their corresponding alleles without any a priori knowledge of HLA-I binding specificity. Our approach recapitulates and refines known motifs for 43 of the most frequent alleles, uncovers new motifs for 9 alleles that up to now had less than five known ligands and provides a scalable framework to incorporate additional HLA peptidomics studies in the future. The refined motifs improve neo-antigen and cancer testis antigen predictions, indicating that unbiased HLA peptidomics data are ideal for in silico predictions of neo-antigens from tumor exome sequencing data. The new motifs further reveal distant modulation of the binding specificity at P2 for some HLA-I alleles by residues in the HLA-I binding site but outside of the B-pocket and we unravel the underlying mechanisms by protein structure analysis, mutagenesis and in vitro binding assays.

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“…THP-1 cells were routinely authenticated by HLA typing using sequence based typing at the HLA-A, B, C, and DRB1 loci from an American Society for Histocompatibility and Immunogenetics (ASHI) accredited laboratory (ASHI#03-5-OK-07-1) ( Lanteri et al, 2011 ). The reported HLA type of the THP-1 cells are HLA-A*02, -B*15, -C*03, -DRB1*01, -DRB1*15 ( Battle et al, 2013 ; Tsuchiya et al, 1980 ). The observed HLA type of the THP-1 cells used in all experiments is HLA-A*02:01, -B*15:11, C*03:03, DRB1*01:01, DRB1*15:01.…”

Section: Methodsmentioning

confidence: 99%

Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

McMurtrey

Trolle

Sansom

et al. 2016

eLife

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HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1–30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F’ pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions.DOI: http://dx.doi.org/10.7554/eLife.12556.001

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Molecular characterisation of the monocytic cell line THP‐1 demonstrates a discrepancy with the documented HLA type

Cited by 15 publications

References 12 publications

Downregulation of MHC Class I Expression by Influenza A and B Viruses

Downregulation of MHC Class I Expression by Influenza A and B Viruses

Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity

Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

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