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HLA class I binding of HBZ determines outcome in HTLV-1 infection.
- Source :
-
PLoS pathogens [PLoS Pathog] 2010 Sep 23; Vol. 6 (9), pp. e1001117. Date of Electronic Publication: 2010 Sep 23. - Publication Year :
- 2010
-
Abstract
- CD8(+) T cells can exert both protective and harmful effects on the virus-infected host. However, there is no systematic method to identify the attributes of a protective CD8(+) T cell response. Here, we combine theory and experiment to identify and quantify the contribution of all HLA class I alleles to host protection against infection with a given pathogen. In 432 HTLV-1-infected individuals we show that individuals with HLA class I alleles that strongly bind the HTLV-1 protein HBZ had a lower proviral load and were more likely to be asymptomatic. We also show that in general, across all HTLV-1 proteins, CD8(+) T cell effectiveness is strongly determined by protein specificity and produce a ranked list of the proteins targeted by the most effective CD8(+) T cell response through to the least effective CD8(+) T cell response. We conclude that CD8(+) T cells play an important role in the control of HTLV-1 and that CD8(+) cells specific to HBZ, not the immunodominant protein Tax, are the most effective. We suggest that HBZ plays a central role in HTLV-1 persistence. This approach is applicable to all pathogens, even where data are sparse, to identify simultaneously the HLA Class I alleles and the epitopes responsible for a protective CD8(+) T cell response.
- Subjects :
- Alleles
Basic-Leucine Zipper Transcription Factors genetics
CD8-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes pathology
CD8-Positive T-Lymphocytes virology
Case-Control Studies
Cohort Studies
Epitopes immunology
Gene Products, tax genetics
Gene Products, tax metabolism
HTLV-I Infections pathology
Humans
Peptide Fragments immunology
Peptide Fragments metabolism
Retroviridae Proteins
Software
T-Lymphocytes, Cytotoxic
Viral Load
Viral Proteins genetics
Basic-Leucine Zipper Transcription Factors metabolism
Genes, MHC Class I physiology
HTLV-I Infections metabolism
HTLV-I Infections virology
Human T-lymphotropic virus 1 physiology
Viral Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 6
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 20886101
- Full Text :
- https://doi.org/10.1371/journal.ppat.1001117