Epitope distribution in ordered and disordered protein regions - Part A. T-cell epitope frequency, affinity and hydropathy
Abstract
Highly disordered protein regions are prevalently hydrophilic, extremely sensitive to proteolysis in vitro, and are expected to be under-represented as T-cell epitopes. The aim of this research was to find out whether disorder and hydropathy prediction methods could help in understanding epitope processing and presentation. According to the pan-specific T-cell epitope predictors NetMHCpan and NetMHCIIpan and 9 publicly available disorder predictors, frequency of epitopes presented by human leukocyte antigens (HLA) class-I or -II was found to be more than 2.5 times higher in ordered than in disordered protein regions (depending on the disorder predictor). Both HLA class-I and HLA class-II binding epitopes are prevalently hydrophilic in disordered and prevalently hydrophobic in ordered protein regions, whereas epitopes recognized by HIA class-II alleles are more hydrophobic than those recognized by HLA class-I. As regards both classes of HLA molecules, high-affinity binding epitopes disp...lay more hydrophobicity than low affinity-binding epitopes (in both ordered and disordered regions). Epitopes belonging to disordered protein regions were not predicted to have poor affinity to HIA class-II molecules, as expected from disorder intrinsic proteolytic instability. The relation of epitope hydrophobicity and order/disorder location was also valid if alleles were grouped according to the HIA class-I and HLA class-II supertypes, except for the class-I supertype A3 in which the main part of recognized epitopes was prevalently hydrophilic. Regarding specific supertypes, the affinity of epitopes belonging to ordered regions varies only slightly (depending on the disorder predictor) compared to the affinity of epitopes in corresponding disordered regions. The distribution of epitopes in ordered and disordered protein regions has revealed that the curves of order-epitope distribution were convex-like while the curves of disorder-epitope distribution were concave-like. The percentage of prevalently hydrophobic epitopes increases with the enhancement of epitope promiscuity level and moving from disordered to ordered regions. These data suggests that reverse vaccinology, oriented towards promiscuous and high-affinity epitopes, is also oriented towards prevalently hydrophobic, ordered regions. The analysis of predicted and experimentally evaluated epitopes of cancer-testis antigen MAGE-A3 has confirmed that the majority of T-cell epitopes, particularly those that are promiscuous or naturally processed, was located in ordered and disorder/order boundary protein regions overlapping hydrophobic regions.
Keywords:
T-cell epitope prediction / Hydropathy prediction / Epitope selection / Disorder predictionSource:
Journal of Immunological Methods, 2014, 406, 83-103Publisher:
- Elsevier, Amsterdam
Funding / projects:
- Automated Reasoning and Data Mining (RS-MESTD-Basic Research (BR or ON)-174021)
- Methods of Numerical and Nonlinear Analysis with Applications (RS-MESTD-Basic Research (BR or ON)-174002)
- Development of new information and communication technologies, based on advanced mathematical methods, with applications in medicine, telecommunications, power systems, protection of national heritage and education (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-44006)
DOI: 10.1016/j.jim.2014.02.012
ISSN: 0022-1759
PubMed: 24614036
WoS: 000337857600010
Scopus: 2-s2.0-84900860532
Collections
Institution/Community
Mašinski fakultetTY - JOUR AU - Mitić, Nenad S. AU - Pavlović, Mirjana D. AU - Jandrlić, Davorka PY - 2014 UR - https://machinery.mas.bg.ac.rs/handle/123456789/2003 AB - Highly disordered protein regions are prevalently hydrophilic, extremely sensitive to proteolysis in vitro, and are expected to be under-represented as T-cell epitopes. The aim of this research was to find out whether disorder and hydropathy prediction methods could help in understanding epitope processing and presentation. According to the pan-specific T-cell epitope predictors NetMHCpan and NetMHCIIpan and 9 publicly available disorder predictors, frequency of epitopes presented by human leukocyte antigens (HLA) class-I or -II was found to be more than 2.5 times higher in ordered than in disordered protein regions (depending on the disorder predictor). Both HLA class-I and HLA class-II binding epitopes are prevalently hydrophilic in disordered and prevalently hydrophobic in ordered protein regions, whereas epitopes recognized by HIA class-II alleles are more hydrophobic than those recognized by HLA class-I. As regards both classes of HLA molecules, high-affinity binding epitopes display more hydrophobicity than low affinity-binding epitopes (in both ordered and disordered regions). Epitopes belonging to disordered protein regions were not predicted to have poor affinity to HIA class-II molecules, as expected from disorder intrinsic proteolytic instability. The relation of epitope hydrophobicity and order/disorder location was also valid if alleles were grouped according to the HIA class-I and HLA class-II supertypes, except for the class-I supertype A3 in which the main part of recognized epitopes was prevalently hydrophilic. Regarding specific supertypes, the affinity of epitopes belonging to ordered regions varies only slightly (depending on the disorder predictor) compared to the affinity of epitopes in corresponding disordered regions. The distribution of epitopes in ordered and disordered protein regions has revealed that the curves of order-epitope distribution were convex-like while the curves of disorder-epitope distribution were concave-like. The percentage of prevalently hydrophobic epitopes increases with the enhancement of epitope promiscuity level and moving from disordered to ordered regions. These data suggests that reverse vaccinology, oriented towards promiscuous and high-affinity epitopes, is also oriented towards prevalently hydrophobic, ordered regions. The analysis of predicted and experimentally evaluated epitopes of cancer-testis antigen MAGE-A3 has confirmed that the majority of T-cell epitopes, particularly those that are promiscuous or naturally processed, was located in ordered and disorder/order boundary protein regions overlapping hydrophobic regions. PB - Elsevier, Amsterdam T2 - Journal of Immunological Methods T1 - Epitope distribution in ordered and disordered protein regions - Part A. T-cell epitope frequency, affinity and hydropathy EP - 103 SP - 83 VL - 406 DO - 10.1016/j.jim.2014.02.012 ER -
@article{ author = "Mitić, Nenad S. and Pavlović, Mirjana D. and Jandrlić, Davorka", year = "2014", abstract = "Highly disordered protein regions are prevalently hydrophilic, extremely sensitive to proteolysis in vitro, and are expected to be under-represented as T-cell epitopes. The aim of this research was to find out whether disorder and hydropathy prediction methods could help in understanding epitope processing and presentation. According to the pan-specific T-cell epitope predictors NetMHCpan and NetMHCIIpan and 9 publicly available disorder predictors, frequency of epitopes presented by human leukocyte antigens (HLA) class-I or -II was found to be more than 2.5 times higher in ordered than in disordered protein regions (depending on the disorder predictor). Both HLA class-I and HLA class-II binding epitopes are prevalently hydrophilic in disordered and prevalently hydrophobic in ordered protein regions, whereas epitopes recognized by HIA class-II alleles are more hydrophobic than those recognized by HLA class-I. As regards both classes of HLA molecules, high-affinity binding epitopes display more hydrophobicity than low affinity-binding epitopes (in both ordered and disordered regions). Epitopes belonging to disordered protein regions were not predicted to have poor affinity to HIA class-II molecules, as expected from disorder intrinsic proteolytic instability. The relation of epitope hydrophobicity and order/disorder location was also valid if alleles were grouped according to the HIA class-I and HLA class-II supertypes, except for the class-I supertype A3 in which the main part of recognized epitopes was prevalently hydrophilic. Regarding specific supertypes, the affinity of epitopes belonging to ordered regions varies only slightly (depending on the disorder predictor) compared to the affinity of epitopes in corresponding disordered regions. The distribution of epitopes in ordered and disordered protein regions has revealed that the curves of order-epitope distribution were convex-like while the curves of disorder-epitope distribution were concave-like. The percentage of prevalently hydrophobic epitopes increases with the enhancement of epitope promiscuity level and moving from disordered to ordered regions. These data suggests that reverse vaccinology, oriented towards promiscuous and high-affinity epitopes, is also oriented towards prevalently hydrophobic, ordered regions. The analysis of predicted and experimentally evaluated epitopes of cancer-testis antigen MAGE-A3 has confirmed that the majority of T-cell epitopes, particularly those that are promiscuous or naturally processed, was located in ordered and disorder/order boundary protein regions overlapping hydrophobic regions.", publisher = "Elsevier, Amsterdam", journal = "Journal of Immunological Methods", title = "Epitope distribution in ordered and disordered protein regions - Part A. T-cell epitope frequency, affinity and hydropathy", pages = "103-83", volume = "406", doi = "10.1016/j.jim.2014.02.012" }
Mitić, N. S., Pavlović, M. D.,& Jandrlić, D.. (2014). Epitope distribution in ordered and disordered protein regions - Part A. T-cell epitope frequency, affinity and hydropathy. in Journal of Immunological Methods Elsevier, Amsterdam., 406, 83-103. https://doi.org/10.1016/j.jim.2014.02.012
Mitić NS, Pavlović MD, Jandrlić D. Epitope distribution in ordered and disordered protein regions - Part A. T-cell epitope frequency, affinity and hydropathy. in Journal of Immunological Methods. 2014;406:83-103. doi:10.1016/j.jim.2014.02.012 .
Mitić, Nenad S., Pavlović, Mirjana D., Jandrlić, Davorka, "Epitope distribution in ordered and disordered protein regions - Part A. T-cell epitope frequency, affinity and hydropathy" in Journal of Immunological Methods, 406 (2014):83-103, https://doi.org/10.1016/j.jim.2014.02.012 . .