HLA class I binding of HBZ determines outcome in HTLV-1 infection.
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 allel...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-09-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001117&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850236202529062912 |
|---|---|
| author | Aidan Macnamara Aileen Rowan Silva Hilburn Ulrich Kadolsky Hiroshi Fujiwara Koichiro Suemori Masaki Yasukawa Graham Taylor Charles R M Bangham Becca Asquith |
| author_facet | Aidan Macnamara Aileen Rowan Silva Hilburn Ulrich Kadolsky Hiroshi Fujiwara Koichiro Suemori Masaki Yasukawa Graham Taylor Charles R M Bangham Becca Asquith |
| author_sort | Aidan Macnamara |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ff52e31081a54d66a76ece4dab95f27c |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-ff52e31081a54d66a76ece4dab95f27c2025-08-20T02:02:01ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-09-0169e100111710.1371/journal.ppat.1001117HLA class I binding of HBZ determines outcome in HTLV-1 infection.Aidan MacnamaraAileen RowanSilva HilburnUlrich KadolskyHiroshi FujiwaraKoichiro SuemoriMasaki YasukawaGraham TaylorCharles R M BanghamBecca AsquithCD8(+) 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001117&type=printable |
| spellingShingle | Aidan Macnamara Aileen Rowan Silva Hilburn Ulrich Kadolsky Hiroshi Fujiwara Koichiro Suemori Masaki Yasukawa Graham Taylor Charles R M Bangham Becca Asquith HLA class I binding of HBZ determines outcome in HTLV-1 infection. PLoS Pathogens |
| title | HLA class I binding of HBZ determines outcome in HTLV-1 infection. |
| title_full | HLA class I binding of HBZ determines outcome in HTLV-1 infection. |
| title_fullStr | HLA class I binding of HBZ determines outcome in HTLV-1 infection. |
| title_full_unstemmed | HLA class I binding of HBZ determines outcome in HTLV-1 infection. |
| title_short | HLA class I binding of HBZ determines outcome in HTLV-1 infection. |
| title_sort | hla class i binding of hbz determines outcome in htlv 1 infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001117&type=printable |
| work_keys_str_mv | AT aidanmacnamara hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT aileenrowan hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT silvahilburn hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT ulrichkadolsky hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT hiroshifujiwara hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT koichirosuemori hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT masakiyasukawa hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT grahamtaylor hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT charlesrmbangham hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection AT beccaasquith hlaclassibindingofhbzdeterminesoutcomeinhtlv1infection |