HLA Class I Binding of HBZ Determines Outcome in HTLV-1 Infection

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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.

Vyšlo v časopise: HLA Class I Binding of HBZ Determines Outcome in HTLV-1 Infection. PLoS Pathog 6(9): e32767. doi:10.1371/journal.ppat.1001117
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001117

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