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HLA class I binding of HBZ determines outcome in HTLV-1 infection.

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.

SUBMITTER: Macnamara A

PROVIDER: S-EPMC2944806 | biostudies-other | 2010 Sep

REPOSITORIES: biostudies-other

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HLA class I binding of HBZ determines outcome in HTLV-1 infection.

Macnamara Aidan A Rowan Aileen A Hilburn Silva S Kadolsky Ulrich U Fujiwara Hiroshi H Suemori Koichiro K Yasukawa Masaki M Taylor Graham G Bangham Charles R M CR Asquith Becca B

PLoS pathogens 20100923 9

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 lowe ...[more]

PMID: 20886101

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HLA class I binding of HBZ determines outcome in HTLV-1 infection.

Publications

HLA class I binding of HBZ determines outcome in HTLV-1 infection.

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