Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle

Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8+ cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and recombi...

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Autores principales: Svitek, Nicholas, Hansen, A.M., Steinaa, Lucilla, Saya, R., Awino, Elias, Nielsen, Morten, Buus, Soren, Nene, Vishvanath M.
Formato: Journal Article
Lenguaje:Inglés
Publicado: Springer 2014
Materias:
Acceso en línea:https://hdl.handle.net/10568/41612
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author Svitek, Nicholas
Hansen, A.M.
Steinaa, Lucilla
Saya, R.
Awino, Elias
Nielsen, Morten
Buus, Soren
Nene, Vishvanath M.
author_browse Awino, Elias
Buus, Soren
Hansen, A.M.
Nene, Vishvanath M.
Nielsen, Morten
Saya, R.
Steinaa, Lucilla
Svitek, Nicholas
author_facet Svitek, Nicholas
Hansen, A.M.
Steinaa, Lucilla
Saya, R.
Awino, Elias
Nielsen, Morten
Buus, Soren
Nene, Vishvanath M.
author_sort Svitek, Nicholas
collection Repository of Agricultural Research Outputs (CGSpace)
description Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8+ cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and recombinant bovine β2-microglobulin from which p-MHC class I tetramers can be derived in ~48 h. We validated a set of p-MHC class I tetramers against a panel of CTL lines specific to seven epitopes on five different antigens of Theileria parva, a protozoan pathogen causing the lethal bovine disease East Coast fever. One of the p-MHC class I tetramers was tested in ex vivo assays and we detected T. parva specific CTL in peripheral blood of cattle at day 15-17 post-immunization with a live parasite vaccine. The algorithm NetMHCpan predicted alternative epitope sequences for some of the T. parva CTL epitopes. Using an ELISA assay to measure peptide-BoLA monomer formation and p-MHC class I tetramers of new specificity, we demonstrate that a predicted alternative epitope Tp229-37 rather than the previously reported Tp227-37 epitope is the correct Tp2 epitope presented by BoLA-6*04101. We also verified the prediction by NetMHCpan that the Tp587-95 epitope reported as BoLA-T5 restricted can also be presented by BoLA-1*02301, a molecule similar in sequence to BoLA-T5. In addition, Tp587-95 specific bovine CTL were simultaneously stained by Tp5-BoLA-1*02301 and Tp5-BoLA-T5 tetramers suggesting that one T cell receptor can bind to two different BoLA MHC class I molecules presenting the Tp587-95 epitope and that these BoLA molecules fall into a single functional supertype.
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spelling CGSpace416122024-05-01T08:20:00Z Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle Svitek, Nicholas Hansen, A.M. Steinaa, Lucilla Saya, R. Awino, Elias Nielsen, Morten Buus, Soren Nene, Vishvanath M. cattle vaccination diagnosis lymphocytes Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8+ cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and recombinant bovine β2-microglobulin from which p-MHC class I tetramers can be derived in ~48 h. We validated a set of p-MHC class I tetramers against a panel of CTL lines specific to seven epitopes on five different antigens of Theileria parva, a protozoan pathogen causing the lethal bovine disease East Coast fever. One of the p-MHC class I tetramers was tested in ex vivo assays and we detected T. parva specific CTL in peripheral blood of cattle at day 15-17 post-immunization with a live parasite vaccine. The algorithm NetMHCpan predicted alternative epitope sequences for some of the T. parva CTL epitopes. Using an ELISA assay to measure peptide-BoLA monomer formation and p-MHC class I tetramers of new specificity, we demonstrate that a predicted alternative epitope Tp229-37 rather than the previously reported Tp227-37 epitope is the correct Tp2 epitope presented by BoLA-6*04101. We also verified the prediction by NetMHCpan that the Tp587-95 epitope reported as BoLA-T5 restricted can also be presented by BoLA-1*02301, a molecule similar in sequence to BoLA-T5. In addition, Tp587-95 specific bovine CTL were simultaneously stained by Tp5-BoLA-1*02301 and Tp5-BoLA-T5 tetramers suggesting that one T cell receptor can bind to two different BoLA MHC class I molecules presenting the Tp587-95 epitope and that these BoLA molecules fall into a single functional supertype. 2014 2014-06-24T10:27:53Z 2014-06-24T10:27:53Z Journal Article https://hdl.handle.net/10568/41612 en Open Access Springer Svitek, N., Hansen, A.M., Steinaa, L., Saya, R., Awino, E., Nielsen, M., Buus, S. and Nene, V. 20014. Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle. Veterinary Research 45:50.
spellingShingle cattle
vaccination
diagnosis
lymphocytes
Svitek, Nicholas
Hansen, A.M.
Steinaa, Lucilla
Saya, R.
Awino, Elias
Nielsen, Morten
Buus, Soren
Nene, Vishvanath M.
Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle
title Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle
title_full Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle
title_fullStr Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle
title_full_unstemmed Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle
title_short Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle
title_sort use of one pot mix and read peptide mhc class i tetramers and predictive algorithms to improve detection of cytotoxic t lymphocyte responses in cattle
topic cattle
vaccination
diagnosis
lymphocytes
url https://hdl.handle.net/10568/41612
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