ArticleJournal of immunology (Baltimore, Md. : 1950)2008
MHC class II presentation of gp100 epitopes in melanoma cells requires the function of conventional endosomes and is influenced by melanosomes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk.Nature communications · 2024Article
- Major histocompatibility complex class II in the tumor microenvironment: functions of nonprofessional antigen-presenting cells.Current opinion in immunology · 2023Review
- The journey from melanocytes to melanoma.Nature reviews. Cancer · 2023Review
- Article
- Melanosome Biogenesis in the Pigmentation of Mammalian Skin.Integrative and comparative biology · 2021Review
- Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- The complex relationship between MITF and the immune system: a Melanoma ImmunoTherapy (response) Factor?Molecular cancer · 2020Review
- High GILT Expression and an Active and Intact MHC Class II Antigen Presentation Pathway Are Associated with Improved Survival in Melanoma.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site.Journal for immunotherapy of cancer · 2019Article
- Spontaneous regression of pancreatic cancer with liver metastases.BMJ case reports · 2019Article
- WIPI1, BAG1, and PEX3 Autophagy-Related Genes Are Relevant Melanoma Markers.Oxidative medicine and cellular longevity · 2018Article
- Study of Exosomes Shed New Light on Physiology of Amyloidogenesis.Cellular and molecular neurobiology · 2016Review
- Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma.Melanoma research · 2016Article
- The Tumor Antigen NY-ESO-1 Mediates Direct Recognition of Melanoma Cells by CD4+ T Cells after Intercellular Antigen Transfer.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Diverse cellular and organismal functions of the lysosomal thiol reductase GILT.Molecular immunology · 2015Review
- Endogenous Antigen Presentation of MHC Class II Epitopes through Non-Autophagic Pathways.Frontiers in immunology · 2015Review
- A novel therapy for melanoma developed in mice: transformation of melanoma into dendritic cells with Listeria monocytogenes.PloS one · 2015Article
- GILT: Shaping the MHC Class II-Restricted Peptidome and CD4(+) T Cell-Mediated Immunity.Frontiers in immunology · 2013Review
- A central role for inducible heat-shock protein 70 in autoimmune vitiligo.Experimental dermatology · 2013Review
- The PKD domain distinguishes the trafficking and amyloidogenic properties of the pigment cell protein PMEL and its homologue GPNMB.Pigment cell & melanoma research · 2013Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Many human solid tumors express MHC class II (MHC-II) molecules, and proteins normally localized to melanosomes give rise to MHC-II-restricted epitopes in melanoma. However, the pathways by which this response occurs have not been defined. We analyzed the processing of one such epitope, gp100(44-59), derived from gp100/Pmel17. In melanomas that have down-regulated components of the melanosomal pathway, but constitutively express HLA-DR*0401, the majority of gp100 is sorted to LAMP-1(high)/MHC-II(+) late endosomes. Using mutant gp100 molecules with altered intracellular trafficking, we demonstrate that endosomal localization is necessary for gp100(44-59) presentation. By depletion of the AP-2 adaptor protein using small interfering RNA, we demonstrate that gp100 protein internalized from the plasma membrane to such endosomes is a major source for gp100(44-59) epitope production. The gp100 trapped in early endosomes gives rise to epitopes that are indistinguishable from those produced in late endosomes but their production is less sensitive to inhibition of lysosomal proteases. In melanomas containing melanosomes, gp100 is underrepresented in late endosomes, and accumulates in stage II melanosomes devoid of MHC-II molecules. The gp100(44-59) presentation is dramatically reduced, and processing occurs entirely in early endosomes or stage I melanosomes. This occurrence suggests that melanosomes are inefficient Ag-processing compartments. Thus, melanoma de-differentiation may be accompanied by increased presentation of MHC-II restricted epitopes from gp100 and other melanosome-localized proteins, leading to enhanced immune recognition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.