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

MacHugh, ND, Connelley, T, Graham, SP, Pelle, R, Formisano, P, Taracha, EL, Ellis, SA, McKeever, DJ, Burrells, A and Morrison, WI (2009) CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity. Eur J Immunol, 39 (9). pp. 2459-2469.

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Abstract

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 beta 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.

Item Type: Article
Subjects : Veterinary Medicine
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
NameEmailORCID
MacHugh, NDUNSPECIFIEDUNSPECIFIED
Connelley, TUNSPECIFIEDUNSPECIFIED
Graham, SPUNSPECIFIEDUNSPECIFIED
Pelle, RUNSPECIFIEDUNSPECIFIED
Formisano, PUNSPECIFIEDUNSPECIFIED
Taracha, ELUNSPECIFIEDUNSPECIFIED
Ellis, SAUNSPECIFIEDUNSPECIFIED
McKeever, DJUNSPECIFIEDUNSPECIFIED
Burrells, AUNSPECIFIEDUNSPECIFIED
Morrison, WIUNSPECIFIEDUNSPECIFIED
Date : September 2009
Identification Number : 10.1002/eji.200939227
Uncontrolled Keywords : Animals, Antigens, Protozoan, CD8-Positive T-Lymphocytes, Cattle, Cell Line, Haplotypes, Histocompatibility Antigens Class I, Polymorphism, Genetic, Receptors, Antigen, T-Cell, alpha-beta, Theileria parva, Theileriasis
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 22 Mar 2016 15:40
Last Modified : 28 Mar 2017 10:58
URI: http://epubs.surrey.ac.uk/id/eprint/810175

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