Letter
Oncology
Tamara Steinfass, Juliane Poelchen, Qian Sun, Giovanni Mastrogiulio, Daniel Novak, Marlene Vierthaler, Sandra Pardo, Aniello Federico, Laura Hueser, Thomas Hielscher, Rafael Carretero, Rienk Offringa, Peter Altevogt, Viktor Umansky, Jochen Utikal
Summary: Melanoma is a deadly form of skin cancer with increasing incidence. Understanding the underlying mechanisms of resistance to treatment can enhance therapy efficacy and success.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
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.
Review
Biochemistry & Molecular Biology
Akhil Shukla, Maryse Cloutier, Madanraj Appiya Santharam, Sheela Ramanathan, Subburaj Ilangumaran
Summary: The immune system constantly monitors and eliminates cancerous cells, with CD8(+) cytotoxic T lymphocytes playing a key role in tumor cell killing. Cancer cells evade immune surveillance by downregulating MHC-I and key proteins of the antigen processing and presentation machinery. NLRC5 has been identified as the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of NLRC5 are common causes of MHC-I defects in cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Raphael Trevizani, Zhen Yan, Jason A. Greenbaum, Alessandro Sette, Morten Nielsen, Bjoern Peters
Summary: An approach to assess the reliability of different metrics for evaluating the performance of MHC class I binding predictors was developed. The study found that using percentile-ranked results improved the stability of the ranks and identified the top-performing tools in the benchmark.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Biochemistry & Molecular Biology
Jorge Alfonso Leon Machado, Viktor Steimle
Summary: CIITA is the master regulator of MHC class II gene expression, functioning as a non-DNA-binding activator through interactions with the MHC enhanceosome complex. In addition to its role in MHC-II gene regulation, CIITA also plays important roles in cancer, viral restriction, and inhibition of virus replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Elena Shklovskaya, Helen Rizos
Summary: It is well acknowledged that the immune system plays a role in controlling tumor growth, but tumors can escape immune surveillance through mechanisms like downregulation or loss of MHC-I molecules. This review examines the dysregulation of MHC-I expression in cancer, the nature of MHC-I-bound antigenic peptides, and discusses therapeutic strategies to address MHC-I deficiency in solid tumors with a focus on NK cells and CD4 T cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Richel J. C. Bilderbeek, Maksim V. Baranov, Geert van den Bogaart, Frans Bianchi
Summary: This study reveals the over-presentation of membrane protein fragments in cytolytic and helper T cell responses. It also demonstrates the evolutionary conservation and lower frequency of mutations in transmembrane helices, suggesting that T cells are more tuned to respond to membrane proteins to avoid evasion by pathogens.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nina Geng, Tuo Hu, Chunbo He
Summary: Immune checkpoint blockade therapies show durable responses in a subset of colorectal cancer patients, but the majority do not respond. Our study suggests that DDX60 may regulate MHC-I expression in colorectal cancer, and targeting DDX60 could potentially improve the efficacy of immunotherapy.
Article
Oncology
Lei Zhan, Junhui Zhang, Jing Zhang, Xiaojing Liu, Suding Zhu, Yuchuan Shi, Yu He, Wenyan Wang, Yijing Wei, Zhenhai Tang, Guo Chen, Bing Wei, Yunxia Cao
Summary: In this study, the researchers found that upregulated autophagy and decreased expression of MHC-I and NLRC5 were associated with endometrial cancer (EC). Inhibition of autophagy was found to suppress MHC-I gene expression. They also discovered that LC3 interacted with NLRC5 to inhibit the NLRC5-mediated MHC-I antigen presentation pathway. These findings suggest that inhibiting LC3 and promoting NLRC5 may be a promising immunotherapy strategy for EC management.
Article
Multidisciplinary Sciences
Jeff D. Colbert, Freidrich M. Cruz, Christina E. Baer, Kenneth L. Rock
Summary: This study reveals a molecular association between Tspan5 and MHC I molecules that is critical for the formation of MHC I nanoclusters and optimal T cell responses to antigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Martin Plasil, Jan Oppelt, Marie Klumplerova, Jana Bubenikova, Leona Vychodilova, Eva Janova, Karla Stejskalova, Jan Futas, Ales Knoll, Agnes Leblond, Andrei D. Mihalca, Petr Horin
Summary: The major histocompatibility complex (MHC) includes class I and II genes that are vital for immune response against pathogens. These genes exhibit high levels of single nucleotide polymorphisms (SNPs) in exons encoding antigen binding sites. This study aimed to investigate the variability of MHC genes, particularly MHC class I physical haplotypes. Using long-range next-generation sequencing, alleles in exon 2 and exon 3 were identified in three genetically distinct horse breeds. A total of 116 allelic variants were found in the MHC class I genes, with 112 being novel. Extensive variability in the MHC region was confirmed, and diversifying and purifying selection were detected in the analyzed MHC class I and II loci.
Article
Multidisciplinary Sciences
Ewa Maria Sroka, Mathilde Lavigne, Marika Pla, Chrysoula Daskalogianni, Maria Camila Tovar-Fernandez, Rodrigo Prado Martins, Benedicte Manoury, Guillaume Darrasse-Jeze, Megane Nascimento, Sebastien Apcher, Robin Fahraeus
Summary: This study found that introducing an MHC class I epitope sequence into the intron of the beta-globin gene in mice can generate immune tolerance. Translation initiation within the intron produces peptides for MHC class I immune tolerance, providing an explanation for the tolerance of alternative tissue-specific splicing by the immune system.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
Biochemical Research Methods
Theo Sturm, Benedikt Sautter, Tobias P. Worner, Stefan Stevanovic, Hans-Georg Rammensee, Oliver Planz, Albert J. R. Heck, Ruedi Aebersold
Summary: This study shows that an optimized mild acid elution (MAE) method can effectively isolate MHC peptide ligands with high purity, providing advantages such as the discovery of unmodified cysteine residues in MHC ligands and enabling high-confidence analysis of post-translational modifications. The results suggest that MAE could be a valuable alternative to MHC immunoaffinity chromatography (MHC-IAC) for suspension cells, offering a cost-effective solution for comprehensive and unbiased characterization of MHC peptide ligands.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Ecology
Piotr Minias, Radoslaw Wlodarczyk, Magdalena Remisiewicz, Ioana Cobzaru, Tomasz Janiszewski
Summary: This study compared the evolution of MHC class I and class II genes in three sister clades of common passerine birds, revealing contrasting evolutionary trajectories of the two MHC classes. MHC class I showed a stronger signature of positive selection and higher allele diversity, while MHC class II exhibited greater allele divergence and stronger recombination signal. The gene copy numbers at both MHC class I and class II evolved via fluctuating selection and drift, with a higher evolutionary rate observed at class I.
