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

PLoS Pathogens

Koichiro Suemori¹  Masaki Yasukawa¹  Hiroshi Fujiwara¹  Charles R. M. Bangham²  Aileen Rowan²  Aidan MacNamara²  Ulrich Kadolsky²  Becca Asquith²  Silva Hilburn³  Graham Taylor³ 

[1] Department of Bioregulatory Medicine, Graduate School of Medicine, Ehime University, and Ehime University Proteomedicine Research Center, Toh-on city, Ehime, Japan;Department of Immunology, Faculty of Medicine, Imperial College, London, United Kingdom;Section of Infectious Diseases, Faculty of Medicine, Imperial College, London, United Kingdom

关键词: HTLV-1;    Cytotoxic T cells;    T cells;    Immune response;    Enzyme-linked immunoassays;    Binding analysis;    Cell binding;    Antigens;   

DOI  :  10.1371/journal.ppat.1001117

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY