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

• Main Authors: Aidan Macnamara, Aileen Rowan, Silva Hilburn, Ulrich Kadolsky, Hiroshi Fujiwara, Koichiro Suemori, Masaki Yasukawa, Graham Taylor, Charles R M Bangham, Becca Asquith
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2010-09-01
• Series: PLoS Pathogens
• Online Access: http://europepmc.org/articles/PMC2944806?pdf=render

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.