Peptide Modification Diminishes HLA Class II-restricted CD4+ T Cell Recognition of Prostate Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. IFN-γ Treatment Induces GILT in Human Prostate Cancer Cells
2.2. GILT Expression Did Not Alter PSMA Levels in Prostate Cancer Cells
2.3. Prostate Cancer Cell EHLA Class II Protein and GILT Insertion Did Not Markedly Alter HLA Protein Expression on the Cell Surface of CWR22 and PC-3 Cells
2.4. GILT Expression Enhances the HLA Class II Mediated Antigen Presentation in PSMA-Expressing Prostate Cancer Cells
2.5. Differential Presentation of PSMA Peptides to CD4+ T Cells: Role of GILT in Enhanced Presentation
2.6. Immunodominant PSMA459 Peptide Contains a Cysteine Residue Which May Become Oxidized and Disrupt Peptide Presentation by CWR22 Cells
2.7. Immunodominant PSMA459 Peptide Becomes Cysteinylated under a Normal Physiological Concentration of Cysteine in Media
3. Discussion
4. Methods and Materials
4.1. Cell Lines and Culture Conditions
4.2. Cell Transduction and Transfection
4.3. Peptides
4.4. Antibodies
4.5. Flow Cytometry
4.6. Western Blot Analysis
4.7. Confocal Microscopy
4.8. Sample Preparation for LC MS/MS
4.9. Mass Spectrometry
4.10. Antigen Presentation Assays
4.11. Enzyme-Linked Immunosorbent Assay
4.12. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
HLA | Human leukocyte antigen |
PSMA | Prostate-specific membrane antigen |
GILT | Gamma–interferon inducible lysosomal thiol reductase |
IMDM | Iscove’s Modified Dulbecco’s Medium |
IFN-γ | Interferon-gamma |
PBMC | Peripheral blood mononuclear cells |
DTT | Dithiothreitol |
ELISA | Enzyme-linked immunosorbent assay |
LC | Liquid chromatography |
MS/MS | Mass spectrometry |
AU | Arbitrary units |
ANOVA | Analysis of variance |
STDEV | Standard deviation |
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Doonan, B.P.; Amria, S.; Bethard, J.R.; Banik, N.L.; Hathaway-Schrader, J.D.; Haque, A. Peptide Modification Diminishes HLA Class II-restricted CD4+ T Cell Recognition of Prostate Cancer Cells. Int. J. Mol. Sci. 2022, 23, 15234. https://doi.org/10.3390/ijms232315234
Doonan BP, Amria S, Bethard JR, Banik NL, Hathaway-Schrader JD, Haque A. Peptide Modification Diminishes HLA Class II-restricted CD4+ T Cell Recognition of Prostate Cancer Cells. International Journal of Molecular Sciences. 2022; 23(23):15234. https://doi.org/10.3390/ijms232315234
Chicago/Turabian StyleDoonan, Bently P., Shereen Amria, Jennifer R. Bethard, Narendra L. Banik, Jessica D. Hathaway-Schrader, and Azizul Haque. 2022. "Peptide Modification Diminishes HLA Class II-restricted CD4+ T Cell Recognition of Prostate Cancer Cells" International Journal of Molecular Sciences 23, no. 23: 15234. https://doi.org/10.3390/ijms232315234