CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity

Although immunodominance of CD8+ T-cell responses is a well-recognised feature of viral infections, its role in responses to more antigenically complex pathogens is less clear. In previous studies we have observed that CD8+ T-cell responses to Theileria parva exhibit different patterns of parasite s...

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Autores principales: MacHugh, Niall D., Connelley, T., Graham, S.P., Pelle, Roger, Formisano, P., Taracha, E.L.N., Ellis, S.A., McKeever, Declan J., Burrells, A., Morrison, W. Ivan
Formato: Journal Article
Lenguaje:Inglés
Publicado: Wiley 2009
Acceso en línea:https://hdl.handle.net/10568/342
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author MacHugh, Niall D.
Connelley, T.
Graham, S.P.
Pelle, Roger
Formisano, P.
Taracha, E.L.N.
Ellis, S.A.
McKeever, Declan J.
Burrells, A.
Morrison, W. Ivan
author_browse Burrells, A.
Connelley, T.
Ellis, S.A.
Formisano, P.
Graham, S.P.
MacHugh, Niall D.
McKeever, Declan J.
Morrison, W. Ivan
Pelle, Roger
Taracha, E.L.N.
author_facet MacHugh, Niall D.
Connelley, T.
Graham, S.P.
Pelle, Roger
Formisano, P.
Taracha, E.L.N.
Ellis, S.A.
McKeever, Declan J.
Burrells, A.
Morrison, W. Ivan
author_sort MacHugh, Niall D.
collection Repository of Agricultural Research Outputs (CGSpace)
description Although immunodominance of CD8+ T-cell responses is a well-recognised feature of viral infections, its role in responses to more antigenically complex pathogens is less clear. In previous studies we have observed that CD8+ T-cell responses to Theileria parva exhibit different patterns of parasite strain specificity in cattle of different MHC genotypes. In the current study, we demonstrated that animals homozygous for the A10 and A18 MHC haplotypes have detectable responses to only one of 5 T. parva antigens. Over 60% of the responding T cells from the A18+ and A10+ animals recognised defined epitopes in the Tp1 and Tp2 antigens, respectively. Comparison of T-cell receptor chain expression profiles of CD8+ T-cell lines and CD8+ T cells harvested ex vivo confirmed that the composition of the T-cell lines was representative of the in vivo memory CD8+ T-cell populations. Analysis of the Tp1 and Tp2 antigens revealed sequence polymorphism, which was reflected by differential recognition by T-cell lines. In conclusion, we have demonstrated a profound immunodominance in the CD8+ T-cell response to T. parva, which we propose is a major determinant of the parasite strain specificity of the response and hence immune protection.
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spelling CGSpace3422023-09-12T13:00:18Z CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity MacHugh, Niall D. Connelley, T. Graham, S.P. Pelle, Roger Formisano, P. Taracha, E.L.N. Ellis, S.A. McKeever, Declan J. Burrells, A. Morrison, W. Ivan Although immunodominance of CD8+ T-cell responses is a well-recognised feature of viral infections, its role in responses to more antigenically complex pathogens is less clear. In previous studies we have observed that CD8+ T-cell responses to Theileria parva exhibit different patterns of parasite strain specificity in cattle of different MHC genotypes. In the current study, we demonstrated that animals homozygous for the A10 and A18 MHC haplotypes have detectable responses to only one of 5 T. parva antigens. Over 60% of the responding T cells from the A18+ and A10+ animals recognised defined epitopes in the Tp1 and Tp2 antigens, respectively. Comparison of T-cell receptor chain expression profiles of CD8+ T-cell lines and CD8+ T cells harvested ex vivo confirmed that the composition of the T-cell lines was representative of the in vivo memory CD8+ T-cell populations. Analysis of the Tp1 and Tp2 antigens revealed sequence polymorphism, which was reflected by differential recognition by T-cell lines. In conclusion, we have demonstrated a profound immunodominance in the CD8+ T-cell response to T. parva, which we propose is a major determinant of the parasite strain specificity of the response and hence immune protection. 2009-09 2010-01-04T14:28:09Z 2010-01-04T14:28:09Z Journal Article https://hdl.handle.net/10568/342 en Open Access Wiley MacHugh, N.D.; Connelley, T.; Graham, S.P.; Pelle, R.; Formisano, P.; Taracha, E.L.; Ellis, S.A.; McKeever, D.J.; Burrells, A.; Morrison, W.I. 2009. CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity. European Journal of Immunology. v. 39(9). p. 2459-2469.
spellingShingle MacHugh, Niall D.
Connelley, T.
Graham, S.P.
Pelle, Roger
Formisano, P.
Taracha, E.L.N.
Ellis, S.A.
McKeever, Declan J.
Burrells, A.
Morrison, W. Ivan
CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity
title CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity
title_full CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity
title_fullStr CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity
title_full_unstemmed CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity
title_short CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity
title_sort cd8 t cell responses to theileria parva are preferentially directed to a single dominant antigen implications for parasite strain specific immunity
url https://hdl.handle.net/10568/342
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