Jul 2026· Current Medical Science· Vol 46, pp. 926 - 945· 0 citations· 168 references
Medicine
TL;DR
An overview of the PLC as a major determinant of tumor immune escape and a potential therapy target is provided and existing or evolving therapeutic approaches to recover/reprogram PLC functions are explored.
A novel method is presented for the expression in eukaryotic cells of secreted peptide exchange–competent class I MHC proteins in their native conformation and it is demonstrated that tetramers produced in this way are equivalent to conventionally produced tetramers for T-cell staining.
V. Ramachandiran, J. Shires, Richard A. Willis et al.· Journal of Immunology· 0 citations
A glycan-dependent chaperone network is defined, finely tuned by a combination of low-micromolar interactions between the constituents, that ensures efficient MHC-I maturation and illustrates fundamental principles of ER protein quality control.
Tim J. Heinke, Amin Fahim, Niko Popovic et al.· EMBO Journal· 0 citations
The main mechanisms of antigen acquisition, endocytic/lysosomal factors controlling MHCII-restricted processing and presentation, and evidence linking lysosomal dysfunction to autoimmunity are explored.
Gabriele Sergio Colangelo, Kyra J Cowan, Federico Riccardi Sirtori et al.· Journal of Immunology· 0 citations
A unified structure-energy-dynamics model explaining how Post-translational modifications function as atomic-level chemical switches in antigen presentation is established, establishing a unified structure-energy-dynamics model explaining how PTMs function as atomic-level chemical switches in antigen presentation.
This review describes the development of pathway-centered mechanistic synthesis across DNA and RNA virus families and further integrate innate immune antagonism, endoplasmic reticulum stress, antigen-presentation competence, cross-presentation limits, and virus-shaped peptide landscapes into a unified framework for understanding viral control of MHC-I output and its translational implications.
Yu Ye, Ying Zhang, Haobing Nie et al.· FEMS Microbiology Reviews· 0 citations
Peptides presented by class-I Human Leukocyte Antigen (HLA-I) proteins provide the basis of immune surveillance. Conversely, reduced surface HLA-I expression is a hallmark of immune evasion in cancers, which confounds the identification of peptide antigens and neoantigens. Here, we outline a system (HLA-Shuttle) for in vitro manipulation of cells with engineered components of the HLA-I processing pathway that improves recovery of the immunopeptidome of immunologically “cold” tumors.
HLA-Shuttle is comprised of an engineered variant of the HLA class I chaperone tapasin that bypasses its native degradation and ER retention signals, enabling improved expression and escape from the ER. HLA-Shuttle provides a continuum of chaperoning activity for HLA-I complexes from their point of assembly in the ER to the cell surface, improving antigen presentation in those cells.
Our data suggest that HLA-Shuttle functions in a multimodal fashion, both enhancing HLA-I complex production in the ER while stabilizing the folded conformation of HLA-I molecules globally. This is evidenced by increased surface expression of HLA-I, while cellular trafficking assays and single particle tracking reveal an extension of their cell-surface lifetimes and microdomain formation, implying an enhancement in their stability. Leveraging this technology, we captured the immunopeptidomes of neuroblastoma cell lines. We observed improved immunoprecipitation of HLA-I complexes, which correlated with a significant expansion of the observable immunopeptidome in immunologically cold neuroblastoma cells. Following bioinformatics analysis to search for therapeutically relevant peptides, we identified multiple novel tumor associated antigens (TAAs) from both known and novel cancer immunotherapy targets.
In conclusion, HLA-Shuttle restores antigen presentation in immunologically cold tumor cells, facilitating identification of TAAs with favorable therapeutic potential.
T32 Fellowship
Classical and Non-Classical Antigen Presenting Cells (APC)
Daniel Hwang, Molly C. Erdman, Santosh Adhikari et al.· Journal of Immunology· 0 citations
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