Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition

Pereira, Branca I.; Devine, Oliver P.; Vukmanovic-Stejic, Milica; Chambers, Emma S.; Subramanian, Priya; Patel, Neil; Virasami, Alex; Sebire, Neil J.; Kinsler, Veronica; Valdovinos, Alexis; LeSaux, Claude Jourdan; Passos, João F.; Antoniou, Antony; Rustin, Malcom H.  A.; Campisi, Judith; Akbar, Arne N.

doi:10.1038/s41467-019-10335-5

Title: Senescent cells evade immune clearance via HLA-E-mediated NK and CD8⁺ T cell inhibition

Journal Article · 02 June 2019 · Nature Communications

DOI: https://doi.org/10.1038/s41467-019-10335-5 · OSTI ID:1546687

Pereira, Branca I. ^[1]; Devine, Oliver P. ^[1]; Vukmanovic-Stejic, Milica ^[1];

^[1]; Subramanian, Priya ^[1]; Patel, Neil ^[1];

^[1]; Sebire, Neil J. ^[1]; Kinsler, Veronica ^[1]; Valdovinos, Alexis ^[2]; LeSaux, Claude Jourdan ^[2]; Passos, João F. ^[3]; Antoniou, Antony ^[4]; Rustin, Malcom H. A. ^[1]; Campisi, Judith ^[5]; Akbar, Arne N. ^[1]

Univ. College London (UCL) (United Kingdom)
Buck Inst. for Research on Aging, Novato, CA (United States)
Newcastle Univ., Newcastle upon Tyne (United Kingdom)
Northumbria Univ., Newcastle upon Tyne (United Kingdom)
Buck Inst. for Research on Aging, Novato, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Senescent cells accumulate in human tissues during ageing and contribute to age-related pathologies. The mechanisms responsible for their accumulation are unclear. Here we show that senescent dermal fibroblasts express the non-classical MHC molecule HLA-E, which interacts with the inhibitory receptor NKG2A expressed by NK and highly differentiated CD8⁺ T cells to inhibit immune responses against senescent cells. HLA-E expression is induced by senescence-associated secretary phenotype-related pro-inflammatory cytokines, and is regulated by p38 MAP kinase signalling in vitro. Consistently, HLA-E expression is increased on senescent cells in human skin sections from old individuals, when compared with those from young, and in human melanocytic nevi relative to normal skin. Lastly, blocking the interaction between HLA-E and NKG2A boosts immune responses against senescent cells in vitro. We thus propose that increased HLA-E expression contributes to persistence of senescent cells in tissues, thereby suggesting a new strategy for eliminating senescent cells during ageing.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1546687

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (60)

Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders Baker, Darren J.; Wijshake, Tobias; Tchkonia, Tamar Nature, Vol. 479, Issue 7372 https://doi.org/10.1038/nature10600	journal	November 2011
The Clinical Potential of Senolytic Drugs Kirkland, James L.; Tchkonia, Tamara; Zhu, Yi Journal of the American Geriatrics Society, Vol. 65, Issue 10 https://doi.org/10.1111/jgs.14969	journal	September 2017
ATM-ATR–dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype Soriani, Alessandra; Zingoni, Alessandra; Cerboni, Cristina Blood, Vol. 113, Issue 15 https://doi.org/10.1182/blood-2008-08-173914	journal	April 2009
Oncogene-Expressing Senescent Melanocytes Up-Regulate MHC Class II, a Candidate Melanoma Suppressor Function van Tuyn, John; Jaber-Hijazi, Farah; MacKenzie, Douglas Journal of Investigative Dermatology, Vol. 137, Issue 10 https://doi.org/10.1016/j.jid.2017.05.030	journal	October 2017
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases Franceschi, C.; Campisi, J. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol. 69, Issue Suppl 1 https://doi.org/10.1093/gerona/glu057	journal	May 2014
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas Xue, Wen; Zender, Lars; Miething, Cornelius Nature, Vol. 445, Issue 7128 https://doi.org/10.1038/nature05529	journal	January 2007
A genomics approach identifies senescence-specific gene expression regulation Lackner, Daniel H.; Hayashi, Makoto T.; Cesare, Anthony J. Aging Cell, Vol. 13, Issue 5 https://doi.org/10.1111/acel.12234	journal	May 2014
The inhibitory NK cell receptor CD94/NKG2A and the activating receptor CD94/NKG2C bind the top of HLA-E through mostly shared but partly distinct sets of HLA-E residues Wada, Haruka; Matsumoto, Naoki; Maenaka, Katsumi European Journal of Immunology, Vol. 34, Issue 1 https://doi.org/10.1002/eji.200324432	journal	January 2004
Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer Rudin, C. M.; Hann, C. L.; Garon, E. B. Clinical Cancer Research, Vol. 18, Issue 11 https://doi.org/10.1158/1078-0432.CCR-11-3090	journal	April 2012
Skin Punch Biopsy Explant Culture for Derivation of Primary Human Fibroblasts Vangipuram, Malini; Ting, Dennis; Kim, Sam Journal of Visualized Experiments, Issue 77 https://doi.org/10.3791/3779	journal	January 2013
NKG2D ligands mediate immunosurveillance of senescent cells Sagiv, Adi; Burton, Dominick G. A.; Moshayev, Zhana Aging, Vol. 8, Issue 2 https://doi.org/10.18632/aging.100897	journal	February 2016
Cellular senescence: Immunosurveillance and future immunotherapy Burton, Dominick G. A.; Stolzing, Alexandra Ageing Research Reviews, Vol. 43 https://doi.org/10.1016/j.arr.2018.02.001	journal	May 2018
Viral Strategies of Immune Evasion Ploegh, H. L. Science, Vol. 280, Issue 5361 https://doi.org/10.1126/science.280.5361.248	journal	April 1998
Senescence of Activated Stellate Cells Limits Liver Fibrosis Krizhanovsky, Valery; Yon, Monica; Dickins, Ross A. Cell, Vol. 134, Issue 4 https://doi.org/10.1016/j.cell.2008.06.049	journal	August 2008
PKC signaling prevents irradiation-induced apoptosis of primary human fibroblasts Bluwstein, A.; Kumar, N.; Léger, K. Cell Death & Disease, Vol. 4, Issue 2 https://doi.org/10.1038/cddis.2013.15	journal	February 2013
An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA Demaria, Marco; Ohtani, Naoko; Youssef, Sameh A. Developmental Cell, Vol. 31, Issue 6 https://doi.org/10.1016/j.devcel.2014.11.012	journal	December 2014
Nk cell Recognition Lanier, Lewis L. Annual Review of Immunology, Vol. 23, Issue 1 https://doi.org/10.1146/annurev.immunol.23.021704.115526	journal	April 2005
Cellular senescence mediates fibrotic pulmonary disease Schafer, Marissa J.; White, Thomas A.; Iijima, Koji Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms14532	journal	February 2017
PKC signaling prevents irradiation-induced apoptosis of primary human fibroblasts Bluwstein, Andrej; Kumar, Nitin; Léger, Karolin ETH Zurich https://doi.org/10.3929/ethz-b-000078934	text	January 2013
The other Janus face of Qa-1 and HLA-E: diverse peptide repertoires in times of stress van Hall, Thorbald; Oliveira, Claudia C.; Joosten, Simone A. Microbes and Infection, Vol. 12, Issue 12-13 https://doi.org/10.1016/j.micinf.2010.07.011	journal	November 2010
A Signal Peptide Derived from hsp60 Binds HLA-E and Interferes with CD94/NKG2A Recognition Michaëlsson, Jakob; Teixeira de Matos, Cristina; Achour, Adnane The Journal of Experimental Medicine, Vol. 196, Issue 11 https://doi.org/10.1084/jem.20020797	journal	December 2002
p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells Iannello, Alexandre; Thompson, Thornton W.; Ardolino, Michele The Journal of Experimental Medicine, Vol. 210, Issue 10 https://doi.org/10.1084/jem.20130783	journal	September 2013
Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells Ruggeri, L.; Urbani, E.; Andre, P. Haematologica, Vol. 101, Issue 5 https://doi.org/10.3324/haematol.2015.135301	journal	December 2015
p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype: p38 regulates the senescence secretory phenotype Freund, Adam; Patil, Christopher K.; Campisi, Judith The EMBO Journal, Vol. 30, Issue 8 https://doi.org/10.1038/emboj.2011.69	journal	March 2011
Characterization of monoclonal antibodies recognizing HLA-G or HLA-E: new tools to analyze the expression of nonclassical HLA class I molecules Menier, Catherine; Saez, Berta; Horejsi, Vaclav Human Immunology, Vol. 64, Issue 3 https://doi.org/10.1016/S0198-8859(02)00821-2	journal	March 2003
A complex secretory program orchestrated by the inflammasome controls paracrine senescence Acosta, Juan Carlos; Banito, Ana; Wuestefeld, Torsten Nature Cell Biology, Vol. 15, Issue 8 https://doi.org/10.1038/ncb2784	journal	June 2013
Interactions between HLA-G and HLA-E in Physiological and Pathological Conditions Morandi, Fabio; Pistoia, Vito Frontiers in Immunology, Vol. 5 https://doi.org/10.3389/fimmu.2014.00394	journal	August 2014
Distinct Functions of Senescence-Associated Immune Responses in Liver Tumor Surveillance and Tumor Progression Eggert, Tobias; Wolter, Katharina; Ji, Juling Cancer Cell, Vol. 30, Issue 4 https://doi.org/10.1016/j.ccell.2016.09.003	journal	October 2016
Regulation of Ligands for the NKG2D Activating Receptor Raulet, David H.; Gasser, Stephan; Gowen, Benjamin G. Annual Review of Immunology, Vol. 31, Issue 1 https://doi.org/10.1146/annurev-immunol-032712-095951	journal	March 2013
Role of non-classical MHC class I molecules in cancer immunosuppression Kochan, Grazyna; Escors, David; Breckpot, Karine OncoImmunology, Vol. 2, Issue 11 https://doi.org/10.4161/onci.26491	journal	November 2013
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence Petrie, Emma J.; Clements, Craig S.; Lin, Jie The Journal of Experimental Medicine, Vol. 205, Issue 3 https://doi.org/10.1084/jem.20072525	journal	March 2008
Relationship between CD107a expression and cytotoxic activity Aktas, Esin; Kucuksezer, Umut Can; Bilgic, Sema Cellular Immunology, Vol. 254, Issue 2 https://doi.org/10.1016/j.cellimm.2008.08.007	journal	January 2009
Human NK cells display major phenotypic and functional changes over the life span: Human NK cell features over the life span Le Garff-Tavernier, Magali; Béziat, Vivien; Decocq, Julie Aging Cell, Vol. 9, Issue 4 https://doi.org/10.1111/j.1474-9726.2010.00584.x	journal	April 2010
Reciprocal age related change in natural killer cell receptors for MHC class I Lutz, Charles T.; Moore, Mikel B.; Bradley, Sarah Mechanisms of Ageing and Development, Vol. 126, Issue 6-7 https://doi.org/10.1016/j.mad.2005.01.004	journal	June 2005
The role of senescent cells in ageing van Deursen, Jan M. Nature, Vol. 509, Issue 7501 https://doi.org/10.1038/nature13193	journal	May 2014
Senescence surveillance of pre-malignant hepatocytes limits liver cancer development Kang, Tae-Won; Yevsa, Tetyana; Woller, Norman Nature, Vol. 479, Issue 7374 https://doi.org/10.1038/nature10599	journal	November 2011
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan Baker, Darren J.; Childs, Bennett G.; Durik, Matej Nature, Vol. 530, Issue 7589 https://doi.org/10.1038/nature16932	journal	February 2016
BRAFE600-associated senescence-like cell cycle arrest of human naevi Michaloglou, Chrysiis; Vredeveld, Liesbeth C. W.; Soengas, Maria S. Nature, Vol. 436, Issue 7051 https://doi.org/10.1038/nature03890	journal	August 2005
Effect of age and CMV on NK cell subpopulations Campos, Carmen; Pera, Alejandra; Sanchez-Correa, Beatriz Experimental Gerontology, Vol. 54 https://doi.org/10.1016/j.exger.2014.01.008	journal	June 2014
Senescence of T Lymphocytes: Implications for Enhancing Human Immunity Akbar, Arne N.; Henson, Sian M.; Lanna, Alessio Trends in Immunology, Vol. 37, Issue 12 https://doi.org/10.1016/j.it.2016.09.002	journal	December 2016
The number of p16INK4a positive cells in human skin reflects biological age: p16INK4a in human skin reflects biological age Waaijer, Mariëtte E. C.; Parish, William E.; Strongitharm, Barbara H. Aging Cell, Vol. 11, Issue 4 https://doi.org/10.1111/j.1474-9726.2012.00837.x	journal	June 2012
KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells Henson, Sian M.; Franzese, Ornella; Macaulay, Richard Blood, Vol. 113, Issue 26 https://doi.org/10.1182/blood-2009-01-199588	journal	June 2009
Enhancing Chemotherapy Efficacy in Pten -Deficient Prostate Tumors by Activating the Senescence-Associated Antitumor Immunity Toso, Alberto; Revandkar, Ajinkya; Di Mitri, Diletta Cell Reports, Vol. 9, Issue 1 https://doi.org/10.1016/j.celrep.2014.08.044	journal	October 2014
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration Ritschka, Birgit; Storer, Mekayla; Mas, Alba Genes & Development, Vol. 31, Issue 2 https://doi.org/10.1101/gad.290635.116	journal	January 2017
Immune surveillance of senescent cells--biological significance in cancer- and non-cancer pathologies Hoenicke, L.; Zender, L. Carcinogenesis, Vol. 33, Issue 6 https://doi.org/10.1093/carcin/bgs124	journal	April 2012
Forging a signature of in vivo senescence Sharpless, Norman E.; Sherr, Charles J. Nature Reviews Cancer, Vol. 15, Issue 7 https://doi.org/10.1038/nrc3960	journal	June 2015
The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression Coppé, Jean-Philippe; Desprez, Pierre-Yves; Krtolica, Ana Annual Review of Pathology: Mechanisms of Disease, Vol. 5, Issue 1 https://doi.org/10.1146/annurev-pathol-121808-102144	journal	January 2010
The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells Lanna, Alessio; Henson, Sian M.; Escors, David Nature Immunology, Vol. 15, Issue 10 https://doi.org/10.1038/ni.2981	journal	August 2014
Identification and characterization of a fibroblast marker: FSP1 Strutz, F. The Journal of Cell Biology, Vol. 130, Issue 2 https://doi.org/10.1083/jcb.130.2.393	journal	July 1995
Senescence of Activated Stellate Cells Limits Liver Fibrosis Krizhanovsky, Valery; Yon, Monica; Dickins, Ross A. Cell, Vol. 135, Issue 1 https://doi.org/10.1016/j.cell.2008.09.015	journal	October 2008
Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation Coupel, Stéphanie; Moreau, Anne; Hamidou, Mohamed Blood, Vol. 109, Issue 7 https://doi.org/10.1182/blood-2006-06-030213	journal	December 2006
Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E Hansen, S. G.; Wu, H. L.; Burwitz, B. J. Science, Vol. 351, Issue 6274 https://doi.org/10.1126/science.aac9475	journal	January 2016
PKC signaling prevents irradiation-induced apoptosis of primary human fibroblasts A., Bluwstein,; N., Kumar,; K., Léger, Nature Publishing Group https://doi.org/10.5167/uzh-76320	text	January 2013
Evaluating the Role of p38 MAPK in the Accelerated Cell Senescence of Werner Syndrome Fibroblasts Davis, Terence; Brook, Amy; Rokicki, Michal Pharmaceuticals, Vol. 9, Issue 2 https://doi.org/10.3390/ph9020023	journal	April 2016
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion Rodier, Francis; Coppé, Jean-Philippe; Patil, Christopher K. Nature Cell Biology, Vol. 11, Issue 8 https://doi.org/10.1038/ncb1909	journal	July 2009
The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor Gasser, Stephan; Orsulic, Sandra; Brown, Eric J. Nature, Vol. 436, Issue 7054 https://doi.org/10.1038/nature03884	journal	July 2005
Senescence and aging: Causes, consequences, and therapeutic avenues McHugh, Domhnall; Gil, Jesús The Journal of Cell Biology, Vol. 217, Issue 1 https://doi.org/10.1083/jcb.201708092	journal	November 2017
Aging, Cellular Senescence, and Cancer Campisi, Judith Annual Review of Physiology, Vol. 75, Issue 1 https://doi.org/10.1146/annurev-physiol-030212-183653	journal	February 2013
The impact of ageing on natural killer cell function and potential consequences for health in older adults Hazeldine, Jon; Lord, Janet M. Ageing Research Reviews, Vol. 12, Issue 4 https://doi.org/10.1016/j.arr.2013.04.003	journal	September 2013
Human NKG2A overrides NKG2C effector functions to prevent autoreactivity of NK cells Béziat, Vivien; Hervier, Baptiste; Achour, Abla Blood, Vol. 117, Issue 16 https://doi.org/10.1182/blood-2010-11-319194	journal	April 2011

Cited By (19)

Additional file 5 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766141.v1	dataset	January 2022
Additional file 3 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766135	dataset	January 2022
Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8 ⁺ T cells in human cutaneous leishmaniasis Covre, Luciana Polaco; Devine, Oliver Patrick; Garcia de Moura, Renan Immunology, Vol. 159, Issue 4 https://doi.org/10.1111/imm.13173	journal	January 2020
Additional file 8 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766150.v1	dataset	January 2022
Virtual Screening of Potential Anti-fatigue Mechanism of Polygonati Rhizoma Based on Network Pharmacology Wang, Ze-Feng; Hu, Ye-Qing; Wu, Qi-Guo Combinatorial Chemistry & High Throughput Screening, Vol. 22, Issue 9 https://doi.org/10.2174/1386207322666191106110615	journal	January 2020
Additional file 10 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766120	dataset	January 2022
Additional file 6 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766144	dataset	January 2022
Skin barrier immunity and ageing Chambers, Emma S.; Vukmanovic‐Stejic, Milica Immunology, Vol. 160, Issue 2 https://doi.org/10.1111/imm.13152	journal	December 2019
Senescence and the Impact on Biodistribution of Different Nanosystems: the Discrepancy on Tissue Deposition of Graphene Quantum Dots, Polycaprolactone Nanoparticle and Magnetic Mesoporous Silica Nanoparticles in Young and Elder Animals dos Reis, Sara Rhaissa Rezende; Pinto, Suyene Rocha; de Menezes, Frederico Duarte Pharmaceutical Research, Vol. 37, Issue 3 https://doi.org/10.1007/s11095-019-2754-9	journal	January 2020
Additional file 7 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766147	dataset	January 2022
Additional file 2 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766132.v1	image	January 2022
Additional file 11 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766123.v1	dataset	January 2022
Additional file 4 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766138.v1	dataset	January 2022
Additional file 9 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766153	dataset	January 2022
Risk profiling using metabolomic characteristics for susceptible individuals of drug-induced liver injury caused by Polygonum multiflorum Zhang, Le; Niu, Ming; Wei, Ai-wu Archives of Toxicology, Vol. 94, Issue 1 https://doi.org/10.1007/s00204-019-02595-3	journal	October 2019
Environmental Exposures and Asthma Development: Autophagy, Mitophagy, and Cellular Senescence Sachdeva, Karan; Do, Danh C.; Zhang, Yan Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.02787	journal	November 2019
Additional file 1 of Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma Xu, Lei; Lu, Yun; Deng, Zhengdong figshare https://doi.org/10.6084/m9.figshare.19766126	image	January 2022
Environmental Exposures and Asthma Development: Autophagy, Mitophagy, and Cellular Senescence Sachdeva, Karan; Do, Danh C.; Zhang, Yan Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.02787	journal	November 2019
Blood autophagy defect causes accelerated non-hematopoietic organ aging Fang, Yixuan; Zhu, Lingjiang; An, Ni Aging, Vol. 11, Issue 14 https://doi.org/10.18632/aging.102086	journal	July 2019

Similar Records

Visualization of the human CD4{sup +} T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/γc{sup null} (NOG) mice by retrogenic expression of the human TCR gene

Journal Article · 2015 · Biochemical and Biophysical Research Communications · OSTI ID:22416875

Takahashi, Takeshi; Katano, Ikumi; Ito, Ryoji; +1 more

Production of human anti-HLA monoclonal antibodies

Conference · 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) · OSTI ID:5417497

Walker, M C; Mercier, F; Roger, J; +1 more

Impact of clonal competition for peptide-MHC complexes on the CD8[superscript +] T-cell repertoire selection in a persistent viral infection

Journal Article · 2008 · Blood · OSTI ID:1006584

Wynn, Katherine K; Fulton, Zara; Cooper, Leanne; +9 more

Related Subjects

60 APPLIED LIFE SCIENCES

Title: Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition

Citation Formats

References (60)

Cited By (19)

Similar Records

Related Subjects

Title: Senescent cells evade immune clearance via HLA-E-mediated NK and CD8⁺ T cell inhibition