The biological and practical significance of antigenic variability in protective T cell responses against Theileria parva

Morrison, W. Ivan

doi:10.1016/j.vetpar.2007.05.007

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…The data presented above indicate that amino acid diversity in the Ta9 40-49 epitope may allow escape from an immune response. Previously, we have shown that A10-restricted CD8 T cell lines from the three A10 ϩ animals examined in the current study exhibit variable killing when tested on infected cloned cell lines derived from the Ankara and Gharb isolates of T. annulata, and preliminary data indicated that cloned CD8 T cell lines exhibit different patterns of killing of these targets (34). Although we proposed that these T cells recognize different target antigens, the results of the present study have demonstrated that all of the A10-restricted CD8 T cell clones from these animals recognize the same epitope in Ta9 (see Table 2).…”

Section: Identification Of T Annulata Antigens and Epitopes Recognizsupporting

confidence: 53%

“…Animals were typed for class I MHC by using a combination of monoclonal antibodies and PCR/ sequencing methods (12,13). Selected animals were immunized with a cloned population of T. annulata (C9) derived from the Ankara isolate (37, 48) as described previously (34). Immunized animals bearing the A10, A14, A15, A18, and A31 MHC haplotypes served as donors of CD8 T cells for antigen screening.…”

Section: Methodsmentioning

confidence: 99%

“…Given the evidence from studies of T. parva that such responses play a key role in immunity (33,34), antigens recognized by T. annulata-specific CD8 T cells represent potential candidates for the development of alternative vaccines. We have previously reported that cattle carrying the A10 class I major histocompatibility complex (MHC) haplotype, immunized with the C9 clone of T. annulata, generate strong A10-restricted CD8 T cell responses that exhibit parasite strain specificity (27).…”

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confidence: 99%

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Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

et al. 2011

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Although parasite strain-restricted CD8 T cell responses have been described for several protozoa, the precise role of antigenic variability in immunity is poorly understood. The tick-borne protozoan parasite Theileria annulata infects leukocytes and causes an acute, often fatal lymphoproliferative disease in cattle. Building on previous evidence of strain-restricted CD8 T cell responses to T. annulata, this study set out to identify and characterize the variability of the target antigens. Three antigens were identified by screening expressed parasite cDNAs with specific CD8 T cell lines. In cattle expressing the A10 class I major histocompatibility complex haplotype, A10-restricted CD8 T cell responses were shown to be focused entirely on a single dominant epitope in one of these antigens (Ta9). Sequencing of the Ta9 gene from field isolates of T. annulata demonstrated extensive sequence divergence, resulting in amino acid polymorphism within the A10-restricted epitope and a second A14-restricted epitope. Statistical analysis of the allelic sequences revealed evidence of positive selection for amino acid substitutions within the region encoding the CD8 T cell epitopes. Sequence differences in the A10-restricted epitope were shown to result in differential recognition by individual CD8 T cell clones, while clones also differed in their ability to recognize different alleles. Moreover, the representation of these clonal specificities within the responding CD8 T cell populations differed between animals. As well as providing an explanation for incomplete protection observed after heterologous parasite challenge of vaccinated cattle, these results have important implications for the choice of antigens for the development of novel subunit vaccines. CD8 T cells have been shown to play a key role in immunity to a variety of intracellular pathogens (65), including a number of protozoan parasites (33,36,38,55). A characteristic feature of CD8 T cell responses is that, in individual hosts, they are often directed against a few dominant epitopes (67). Consequently, mutations in sites encoding these epitopes can result in escape from immune recognition. This is well established as an important phenomenon in infections with some RNA viruses that exhibit a high rate of mutation, most notably, HIV-1 (18, 26, 39). Parasite strain-restricted CD8 T cell responses have also been reported for several protozoan infections, including human malaria and theileriosis in cattle (15,17,35). In the case of Theileria parva, variation between animals in the strain specificity of CD8 T cell responses has been shown to correlate with incomplete cross-protection between parasite strains (54). These observations suggest that polymorphism of the target parasite antigens may have arisen as a result of CD8 T cell imposed immune selection.The bovine tick-borne parasites Theileria parva and T. annulata infect and transform leukocytes, causing acute lymphoproliferative diseases that result in high levels of mortality and heavy production losses (25)....

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Section: Identification Of T Annulata Antigens and Epitopes Recognizsupporting

confidence: 53%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

et al. 2011

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“…Consequently, parasite populations, although genotypically diverse, are likely to show complex patterns of antigenic relatedness. I have proposed that this population structure, coupled with focusing of the CD8 T cell response on dominant polymorphic antigens, accounts for the observed patterns of incomplete cross-protection between parasite strains (Morrison, 2007). Although genetic exchange can generate enormous genotypic diversity, it may (depending on the extent of polymorphism in the antigens) increase the likelihood that any pair of parasite clones will share alleles of some of the dominant antigens.…”

Section: M M U N O D O M I N a N C E A N D G E N E T I C E X C H A mentioning

confidence: 99%

Progress towards understanding the immunobiology ofTheileriaparasites

Morrison

2009

Parasitology

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The pathogenic Theileria species Theileria parva and T. annulata infect bovine leukocytes and erythrocytes causing acute, often fatal lymphoproliferative diseases in cattle. The parasites are of interest not only because of their economic importance as pathogens, but also because of their unique ability to transform the leukocytes they infect. The latter property allows parasitized leukocytes to be cultured as continuously growing cell lines in vitro, thus providing an amenable in vitro system to study the parasite/host cell relationship and parasite-specific cellular immune responses. This paper summarizes important advances in knowledge of the immunobiology of these parasites over the last 40 years, focusing particularly on areas of relevance to vaccination.

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“…The mixture, known as the “Muguga cocktail”, is the basis of a commercial ITM vaccine, which appears to provide broad protection against T. parva in the field [ 9 , 10 ]. Strain specificity of the CTL response has also been described but mostly in context of CTL clones [ 5 , 11 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic T lymphocytes from cattle sharing the same MHC class I haplotype and immunized with live Theileria parva sporozoites differ in antigenic specificity

et al. 2018

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ObjectivesThe objective of this study was to assess whether cytotoxic T cells (CTL) generated by the live vaccine, known as “ITM Muguga cocktail”, which is used for the cattle disease East Cost fever (ECF) in Sub-Saharan Africa, showed a broad reactivity against many different strains of the causative parasite Theileria parva. We also assessed whether immune responses were similar in cattle expressing the same MHC class I haplotypes.ResultsThe antigenic specificity of CTL from MHC class I-matched cattle vaccinated with the Muguga cocktail were different. Three cattle of MHC class I haplotype A18, one A18/A19 and two haploidentical (A18v/A12) animals, showed differential recognition of autologous cells infected with a panel of T. parva isolates. This could have implications in the field where certain strains could break through the vaccine. Furthermore, neither of the haploidentical cattle recognized the CTL epitope (Tp1214–224), presented by the A18 haplotype, in contrast to the third animal, showing differences in immunodominance in animals of the same haplotype A18. This suggests that the CTL specificities following immunization with the Muguga cocktail can vary even between haploidentical individuals and that some parasite strains may break through immunity generated by the Muguga cocktail.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3145-8) contains supplementary material, which is available to authorized users.

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The biological and practical significance of antigenic variability in protective T cell responses against Theileria parva

Cited by 8 publications

References 58 publications

Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

Progress towards understanding the immunobiology ofTheileriaparasites

Cytotoxic T lymphocytes from cattle sharing the same MHC class I haplotype and immunized with live Theileria parva sporozoites differ in antigenic specificity

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