PMID- 29084996
OWN - NLM
STAT- MEDLINE
DCOM- 20190701
LR  - 20190701
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Oct 30
TI  - Host genotype and time dependent antigen presentation of viral peptides: 
      predictions from theory.
PG  - 14367
LID - 10.1038/s41598-017-14415-8 [doi]
LID - 14367
AB  - The rate of progression of HIV infected individuals to AIDS is known to vary with 
      the genotype of the host, and is linked to their allele of human leukocyte 
      antigen (HLA) proteins, which present protein degradation products at the cell 
      surface to circulating T-cells. HLA alleles are associated with Gag-specific 
      T-cell responses that are protective against progression of the disease. While 
      Pol is the most conserved HIV sequence, its association with immune control is 
      not as strong. To gain a more thorough quantitative understanding of the factors 
      that contribute to immunodominance, we have constructed a model of the 
      recognition of HIV infection by the MHC class I pathway. Our model predicts 
      surface presentation of HIV peptides over time, demonstrates the importance of 
      viral protein kinetics, and provides evidence of the importance of Gag peptides 
      in the long-term control of HIV infection. Furthermore, short-term dynamics are 
      also predicted, with simulation of virion-derived peptides suggesting that 
      efficient processing of Gag can lead to a 50% probability of presentation within 
      3 hours post-infection, as observed experimentally. In conjunction with epitope 
      prediction algorithms, this modelling approach could be used to refine 
      experimental targets for potential T-cell vaccines, both for HIV and other 
      viruses.
FAU - Eccleston, R Charlotte
AU  - Eccleston RC
AD  - Centre for Computational Science, Department of Chemistry, University College 
      London, London, WC1H 0AJ, UK.
AD  - CoMPLEX, University College London, London, WC1E 6BT, UK.
FAU - Coveney, Peter V
AU  - Coveney PV
AUID- ORCID: 0000-0002-8787-7256
AD  - Centre for Computational Science, Department of Chemistry, University College 
      London, London, WC1H 0AJ, UK.
AD  - CoMPLEX, University College London, London, WC1E 6BT, UK.
FAU - Dalchau, Neil
AU  - Dalchau N
AUID- ORCID: 0000-0002-4872-6914
AD  - Microsoft Research, Cambridge, CB1 2FB, UK. ndalchau@microsoft.com.
LA  - eng
GR  - MR/L016311/1/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171030
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Epitopes)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Gene Products, gag)
RN  - 0 (HIV Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Peptides)
RN  - 0 (gag Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Algorithms
MH  - Antigen Presentation
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Computer Simulation
MH  - Epitopes/immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Forecasting/*methods
MH  - Gene Products, gag/genetics/immunology
MH  - Genes, MHC Class I/genetics/immunology
MH  - Genotype
MH  - HIV Antigens/immunology
MH  - HIV Infections/virology
MH  - HIV-1/genetics/*immunology
MH  - Histocompatibility Antigens Class II/genetics
MH  - Humans
MH  - Immunodominant Epitopes/*immunology
MH  - Peptides/genetics
MH  - gag Gene Products, Human Immunodeficiency Virus/genetics
PMC - PMC5662608
COIS- The authors declare that they have no competing interests.
EDAT- 2017/11/01 06:00
MHDA- 2019/07/02 06:00
PMCR- 2017/10/30
CRDT- 2017/11/01 06:00
PHST- 2017/02/16 00:00 [received]
PHST- 2017/10/11 00:00 [accepted]
PHST- 2017/11/01 06:00 [entrez]
PHST- 2017/11/01 06:00 [pubmed]
PHST- 2019/07/02 06:00 [medline]
PHST- 2017/10/30 00:00 [pmc-release]
AID - 10.1038/s41598-017-14415-8 [pii]
AID - 14415 [pii]
AID - 10.1038/s41598-017-14415-8 [doi]
PST - epublish
SO  - Sci Rep. 2017 Oct 30;7(1):14367. doi: 10.1038/s41598-017-14415-8.