Adoptive transfer of immunity to Theileria parva inthe CD8+ fraction of responding efferent lymph.

McKeever, Declan J.; Taracha, Evans; Innes, Elisabeth A.; MacHugh, Niall D.; Awino, Elias; Goddeeris, Bruno; Morrison, W. Ivan

doi:10.1073/pnas.91.5.1959

Cited by 115 publications

(108 citation statements)

References 23 publications

(18 reference statements)

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…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).…”

mentioning

confidence: 99%

“…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).…”

mentioning

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).…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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)....

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…Manufacture and delivery of the live ECF vaccine is difficult to sustain, but it has enabled elucidation of the dominant protective immune response against the disease. Kinetic and adoptive cell transfer studies (5,6) have demonstrated that protection of cattle is mediated by MHC class I-restricted CD8 ϩ cytotoxic T lymphocytes (CTL) that destroy schizontinfected lymphocytes, the pathogenic life-cycle stage of T. parva. In addition, there is a strong correlation between the specificity of the CTL response and cross-immunity profiles of distinct parasite strains (2).…”

mentioning

confidence: 99%

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

Graham

Pellé

Honda

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

115

131

View full text Add to dashboard Cite

East Coast fever, caused by the tick-borne intracellular apicomplexan parasite Theileria parva, is a highly fatal lymphoproliferative disease of cattle. The pathogenic schizont-induced lymphocyte transformation is a unique cancer-like condition that is reversible with parasite removal. Schizont-infected cell-directed CD8 ؉ cytotoxic T lymphocytes (CTL) constitute the dominant protective bovine immune response after a single exposure to infection. However, the schizont antigens targeted by T. parva-specific CTL are undefined. Here we show the identification of five candidate vaccine antigens that are the targets of MHC class I-restricted CD8 ؉ CTL from immune cattle. CD8 ؉ T cell responses to these antigens were boosted in T. parva-immune cattle resolving a challenge infection and, when used to immunize naïve cattle, induced CTL responses that significantly correlated with survival from a lethal parasite challenge. These data provide a basis for developing a CTL-targeted anti-East Coast fever subunit vaccine. In addition, orthologs of these antigens may be vaccine targets for other apicomplexan parasites.cattle ͉ East Coast fever ͉ immunoscreening ͉ protozoan parasite ͉ vaccination A single inoculation with a potentially lethal dose of Theileria parva sporozoites and simultaneous treatment with a longacting oxytetracycline induces solid immunity to homologous and, in certain instances, heterologous parasite challenge (1, 2). This methodology has been adopted as a live vaccine for the control of East Coast fever (ECF) (3). The long-lasting immunity to ECF contrasts with the partial immunity to malaria that develops after only several years of exposure to T. parva-related Plasmodium spp. (4). Manufacture and delivery of the live ECF vaccine is difficult to sustain, but it has enabled elucidation of the dominant protective immune response against the disease. Kinetic and adoptive cell transfer studies (5, 6) have demonstrated that protection of cattle is mediated by MHC class I-restricted CD8 ϩ cytotoxic T lymphocytes (CTL) that destroy schizontinfected lymphocytes, the pathogenic life-cycle stage of T. parva. In addition, there is a strong correlation between the specificity of the CTL response and cross-immunity profiles of distinct parasite strains (2). The identification of schizont antigens targeted by CTL from T. parva-immune cattle has been elusive but should pave the way for the development of a subunit vaccine against ECF and provide a long-term solution to a socioeconomically important constraint to livestock agriculture in Africa (7). We adopted two approaches to antigen identification, both dependent on screening of transiently transfected antigenpresenting cells with fully characterized CTL (8, 9) from live vaccine-immunized cattle of diverse bovine leukocyte antigen (BoLA) MHC class I genotypes. First, in a targeted gene approach, we immunoscreened genes that were predicted by using preliminary sequence data from one of the four T. parva chromosomes (10) to contain a secretion signal. The approach was ...

show abstract

“…Evidence that immunity to T. parva is mediated by MHC class I-restricted CD8 T cells specific for the intralymphocytic schizont stage of the parasite is based on observations on the kinetics of CD8 T-cell responses (15) and the demonstration that immunity can be transferred adoptively with CD8 T-cellenriched populations from immune cattle (13). Parasite-specific CD8 T-cell responses induced by immunization with a single parasite strain show differential degrees of recognition of heterologous parasite strains, and a close correlation between the specificity of CD8 T-cell responses and the crossimmunity profiles of distinct parasite strains has been observed previously (8,19).…”

mentioning

confidence: 99%

Characterization of the Fine Specificity of Bovine CD8 T-Cell Responses to Defined Antigens from the Protozoan ParasiteTheileria parva

et al. 2008

View full text Add to dashboard Cite

Immunity against the bovine intracellular protozoan parasite Theileria parva has been shown to be mediated by CD8 T cells. Six antigens targeted by CD8 T cells from T. parva-immune cattle of different major histocompatibility complex (MHC) genotypes have been identified, raising the prospect of developing a subunit vaccine. To facilitate further dissection of the specificity of protective CD8 T-cell responses and to assist in the assessment of responses to vaccination, we set out to identify the epitopes recognized in these T. parva antigens and their MHC restriction elements. Nine epitopes in six T. parva antigens, together with their respective MHC restriction elements, were successfully identified. Five of the cytotoxic-T-lymphocyte epitopes were found to be restricted by products of previously described alleles, and four were restricted by four novel restriction elements. Analyses of CD8 T-cell responses to five of the epitopes in groups of cattle carrying the defined restriction elements and immunized with live parasites demonstrated that, with one exception, the epitopes were consistently recognized by animals of the respective genotypes. The analysis of responses was extended to animals immunized with multiple antigens delivered in separate vaccine constructs. Specific CD8 T-cell responses were detected in 19 of 24 immunized cattle. All responder cattle mounted responses specific for antigens for which they carried an identified restriction element. By contrast, only 8 of 19 responder cattle displayed a response to antigens for which they did not carry an identified restriction element. These data demonstrate that the identified antigens are inherently dominant in animals with the corresponding MHC genotypes.

show abstract

Adoptive transfer of immunity to Theileria parva inthe CD8+ fraction of responding efferent lymph.

Cited by 115 publications

References 23 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

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

Characterization of the Fine Specificity of Bovine CD8 T-Cell Responses to Defined Antigens from the Protozoan ParasiteTheileria parva

Contact Info

Product

Resources

About