Article
Cell Biology
Adi Nagler, Shelly Kalaora, Chaya Barbolin, Anastasia Gangaev, Steven L. C. Ketelaars, Michal Alon, Joy Pai, Gil Benedek, Yfat Yahalom-Ronen, Noam Erez, Polina Greenberg, Gal Yagel, Aviyah Peri, Yishai Levin, Ansuman T. Satpathy, Erez Bar-Haim, Nir Paran, Pia Kvistborg, Yardena Samuels
Summary: This study identified SARS-CoV-2-derived peptides presented by HLA-I and HLA-II molecules, some of which are immunogenic, potentially aiding in the development of next-generation SARS-CoV-2 vaccines.
Article
Biochemistry & Molecular Biology
Gad Armony, Albert J. R. Heck, Wei Wu
Summary: The study reveals that HLA molecules exhibit various modes of interactions on the plasma membrane, demonstrating their ability to be densely packed in this environment.
MOLECULAR IMMUNOLOGY
(2021)
Article
Immunology
Mark N. Lee, Matthew Meyerson
Summary: This study introduces a high-throughput epitope identification system that combines T cell-secreted cytokines capture, cell sorting, and next-generation sequencing to identify new class I- and class II-restricted epitopes. The technology successfully validated known viral, neoepitope, and autoimmune epitope-specific TCR targets, as well as discovered new epitopes encoded by the human cytomegalovirus genome. This cytokine capture-based assay enables pooled screening of thousands of encoded peptides for epitope discovery and may lead to identification of HLA-epitope-TCR complexes relevant to disease control, etiology, or treatment.
SCIENCE IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Patrick C. Lee, Susan Klaeger, Phuong M. Le, Keegan Korthauer, Jingwei Cheng, Varsha Ananthapadmanabhan, Thomas C. Frost, Jonathan D. Stevens, Alan Y. L. Wong, J. Bryan Iorgulescu, Anna Y. Tarren, Vipheaviny A. Chea, Isabel P. Carulli, Camilla K. Lemvigh, Christina B. Pedersen, Ashley K. Gartin, Siranush Sarkizova, Kyle T. Wright, Letitia W. Li, Jason Nomburg, Shuqiang Li, Teddy Huang, Xiaoxi Liu, Lucas Pomerance, Laura M. Doherty, Annie M. Apffel, Luke J. Wallace, Suzanna Rachimi, Kristen D. Felt, Jacquelyn O. Wolff, Elizabeth Witten, Wandi Zhang, Donna Neuberg, William J. Lane, Guanglan Zhang, Lars R. Olsen, Manisha Thakuria, Scott J. Rodig, Karl R. Clauser, Gabriel J. Starrett, John G. Doench, Sara J. Buhrlage, Steven A. Carr, James A. DeCaprio, Catherine J. Wu, Derin B. Keskin
Summary: This study reveals transcriptional suppression of HLA-I antigen presentation in Merkel cell carcinoma and identifies MYCL, PRC1.1, and USP7 as regulators in this process.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biology
Eli Olson, Theadora Ceccarelli, Malini Raghavan
Summary: The extreme polymorphisms of HLA class I proteins enable diverse peptide presentation, and the endo-lysosomes in moDCs play a role in the presentation of HLA class I molecules. HLA-B allotypes display varying responses to disruption of the endo-lysosomal pH, with HLA-B*08:01 being more resistant and HLA-B*35:01 being more sensitive. The degree of endo-lysosomal assembly dictates constitutive HLA class I expression and affects the efficiency of cross-presentation.
Article
Immunology
Zhansong Lin, Arman A. Bashirova, Mathias Viard, Lee Garner, Max Quastel, Maya Beiersdorfer, Wojciech K. Kasprzak, Marjan Akdag, Yuko Yuki, Pedro Ojeda, Sudipto Das, Thorkell Andresson, Vivek Naranbhai, Amir Horowitz, Andrew J. McMichael, Angelique Hoelzemer, Geraldine M. Gillespie, Wilfredo F. Garcia-Beltran, Mary Carrington
Summary: Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors. Carrington and colleagues provide comprehensive analysis of classical HLA class I SP variants and show that these can determine CD94/NKG2-HLA-E engagement. The systematic, quantitative approach described herein will facilitate development of prediction algorithms for accurately measuring the impact of CD94/NKG2-HLA-E interactions in disease resistance/susceptibility.
Article
Cell Biology
Clarety Kaseke, Ryan J. Park, Nishant K. Singh, Dylan Koundakjian, Arman Bashirova, Wilfredo F. Garcia Beltran, Overbeck C. Takou Mbah, Jiaqi Ma, Fernando Senjobe, Jonathan M. Urbach, Anusha Nathan, Elizabeth J. Rossin, Rhoda Tano-Menka, Ashok Khatri, Alicja Piechocka-Trocha, Michael T. Waring, Michael E. Birnbaum, Brian M. Baker, Mary Carrington, Bruce D. Walker, Gaurav D. Gaiha
Summary: The study found that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules compared to subdominant epitopes, and HLA class-I-peptide stability is strongly correlated with overall immunodominance hierarchies. Additionally, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions.
Article
Oncology
Yvette Robbins, Jay Friedman, Jason Redman, Cem Sievers, Wiem Lassoued, James L. Gulley, Clint T. Allen
Summary: This study found that expression of tumor cell HLA class I is correlated with pathologic response in patients with primary untreated head and neck cancer. Furthermore, the pre-treatment level of tumor cell HLA class I expression is associated with the development of pathologic response.
Article
Chemistry, Analytical
Apresio K. Fajrial, Kun Liu, Yu Gao, Junhao Gu, Richard Lakerveld, Xiaoyun Ding
Summary: Characterization of physical biomarkers of cells through osmotic swelling can evaluate unique swelling dynamics of different cell types with high accuracy. This method can also detect changes in cellular mechanical properties due to cytoskeleton disruption, offering potential applications in both biological studies and clinical practice. Its simplicity makes swelling dynamics an invaluable label-free physical biomarker for cells.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Yue Shen, Jerry M. Parks, Jeremy C. Smith
Summary: The HLA-Clus package provides a clustering method for HLA Class I alleles based on their 3D structural similarity. It can be used in HLA functional studies and disease association studies.
BMC BIOINFORMATICS
(2023)
Article
Cell Biology
Maria Rosa Moya-Quiles, Manuel Muro
Summary: Two novel HLA class I alleles, HLA-B*35:572 and HLA-C*04:491, were detected using next-generation sequencing.
Article
Oncology
Saskia J. J. Santegoets, Marij J. P. Welters, Deborah S. S. Schrikkema, Manon R. R. Freriks, Hanna Kok, Bianca Weissbrich, Anouk van den Branden, Carsten Linnemann, Ton N. N. Schumacher, Sabina Adhikary, Gavin Bendle, Sjoerd H. H. van der Burg
Summary: Immunotherapies targeting tumor-specific targets focus on expanding and activating T cells against neoantigens or oncogenic viruses, such as the human papilloma virus type 16 (HPV16). In this study, CD8(+) T cell epitopes in HPV16-induced tumors were identified using multimers and a functional screening platform. Specific HLA-peptide combinations dominated the T cell response in patients expressing these HLA alleles. T cell receptors reactive to HLA class I-restricted peptides could be isolated and shown to have tumor reactivity. These tumor-reactive T cell receptors can potentially be used in adoptive cell transfer approaches for treating HPV16-induced cancers.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Tomoyo Shinkawa, Serina Tokita, Munehide Nakatsugawa, Yasuhiro Kikuchi, Takayuki Kanaseki, Toshihiko Torigoe
Summary: CD8(+) T cells can recognize mutation-derived neoantigens presented by HLA class I molecules, distinguishing cancer cells from normal cells. However, only a small portion of nonsynonymous somatic mutations produce clinically relevant neoantigens. Immunodominant neoantigens were identified using naive CD8(+) T cells from healthy donors, with T cell responses varying across individuals and biased towards variants with significant structural changes. Structural dissimilarity, gene expression levels, HLA binding affinity, and stability are important determinants for prioritizing the immunogenicity of non-anchor-type neoantigens.
Article
Oncology
Junko Matsuzaki, Shashikant Lele, Kunle Odunsi, Takemasa Tsuji
Summary: Adoptive cell therapy (ACT) is a promising immunotherapy that provides cancer antigen-specific effector T cells for cancer patients. This study characterized the immunogenicity of CLDN6 in ovarian cancer patients and identified specific TCR genes from CD8(+) and CD4(+) T cells, which are important for the treatment of ovarian and other solid tumors expressing CLDN6.
Article
Immunology
Marlieke L. M. Jongsma, Antonius A. de Waard, Matthijs Raaben, Tao Zhang, Birol Cabukusta, Rene Platzer, Vincent A. Blomen, Anastasia Xagara, Tamara Verkerk, Sophie Bliss, Xiangrui Kong, Carolin Gerke, Lennert Janssen, Elmer Stickel, Stephanie Holst, Rosina Plomp, Arend Mulder, Soldano Ferrone, Frans H. J. Claas, Mirjam H. M. Heemskerk, Marieke Griffioen, Anne Halenius, Hermen Overkleeft, Johannes B. Huppa, Manfred Wuhrer, Thijn R. Brummelkamp, Jacques Neefjes, Robbert M. Spaapen
Summary: HLA class I glycoproteins play a crucial role in driving immune responses by presenting antigens, but tumors and pathogens often exploit this process for immune evasion. Through genome-wide screens, it was discovered that the cell surface glycosphingolipid repertoire determines effective HLA-I antigen presentation. Inhibition of GSL synthesis may represent a potential therapeutic target in cancer, infection, and autoimmunity, offering a promising avenue for immune modulation.
Article
Immunology
Yi-Ping Jin, Nicole M. Valenzuela, Xiaohai Zhang, Enrique Rozengurt, Elaine F. Reed
JOURNAL OF IMMUNOLOGY
(2018)
Article
Cell Biology
Mary E. Ziegler, Yi-Ping Jin, Steven H. Young, Enrique Rozengurt, Elaine F. Reed
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2012)
Article
Surgery
Y. -P. Jin, N. M. Valenzuela, M. E. Ziegler, E. Rozengurt, E. F. Reed
AMERICAN JOURNAL OF TRANSPLANTATION
(2014)
Article
Hematology
Stephanie A. Popson, Mary E. Ziegler, Xiaofang Chen, Matthew T. Holderfield, Cameron I. Shaaban, Ashley H. Fong, Katrina M. Welch-Reardon, Jackie Papkoff, Christopher C. W. Hughes
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2014)
Article
Immunology
Fang Li, Xiaohai Zhang, Yi-Ping Jin, Arend Mulder, Elaine F. Reed
Article
Immunology
Peter T. Jindra, Yi-Ping Jin, Enquire Rozengurt, Elaine F. Reed
JOURNAL OF IMMUNOLOGY
(2008)
Article
Immunology
Mary E. Ziegler, Tingchao Chen, James F. LeBlanc, Xuelian Wei, David W. Gjertson, Ker-Chau Li, Mazdak A. Khalighi, Charles R. Lassman, Jeffrey L. Veale, H. Albin Gritsch, Elaine F. Reed
Article
Gastroenterology & Hepatology
Rebecca A. Sosa, Allyson Q. Terry, Fady M. Kaldas, Yi-Ping Jin, Maura Rossetti, Takahiro Ito, Fang Li, Richard S. Ahn, Bita V. Naini, Victoria M. Groysberg, Ying Zheng, Antony Aziz, Jessica Nevarez-Mejia, Ali Zarrinpar, Ronald W. Busuttil, David W. Gjertson, Jerzy W. Kupiec-Weglinski, Elaine F. Reed
Summary: The study identified disulfide-HMGB1 as a mechanistic biomarker and therapeutic target for minimizing sterile inflammation during human liver ischemia-reperfusion injury.
Article
Immunology
Tarique Anwar, James Sinnett-Smith, Yi-Ping Jin, Elaine F. Reed, Enrique Rozengurt
JOURNAL OF IMMUNOLOGY
(2020)
Article
Immunology
Yi-Ping Jin, Jessica Nevarez-Mejia, Allyson Q. Terry, Rebecca A. Sosa, Sebastiaan Heidt, Nicole M. Valenzuela, Enrique Rozengurt, Elaine F. Reed
Summary: Donor-specific HLA antibodies stimulate the formation of complexes between TLR4 and HLA I on ECs, leading to EC activation and recruitment of monocytes. Knockdown of TLR4 or MyD88 inhibits P-selectin expression, von Willebrand factor release, and monocyte recruitment on ECs stimulated by HLA I antibodies.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Surgery
Sahar Salehi, Rebecca A. Sosa, Yi-Ping Jin, Shoichi Kageyama, Michael C. Fishbein, Enrique Rozengurt, Jerzy W. Kupiec-Weglinski, Elaine F. Reed
AMERICAN JOURNAL OF TRANSPLANTATION
(2018)