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

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 β 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.

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

“…The failure to detect recognition of Ta9 by CD8 T cell lines restricted by three other class I MHC haplotypes (A15, A18, and A31) confirms that dominance of this antigen is dependent on host MHC genotype. MHC related hierarchy in dominance of epitopes is consistent with findings for T. parva in cattle (28) and is a well-recognized feature of CD8 T cell responses to viruses in humans and mice (2, 56, 66). a Origin of parasites and T cell clones described in Table 4.…”

Escape from CD8+ T Cell Response by Natural Variants of an Immunodominant Epitope from Theileria parva Is Predominantly Due to Loss of TCR Recognition

“…Subsequent studies of responses to defined T. parva Ags recognized by CD8 + T cells from immune cattle have confirmed the immunodominant nature of the response (30)(31)(32). We have shown that single epitopes in the Tp1 and Tp2 Ags account for .60% of the CD8 + T cell response in animals homozygous for the A18 and A10 class I haplotypes, respectively (33). Moreover, recent analyses of field isolates of T. parva confirmed that both of these epitopes are polymorphic.…”

“…Sequencing of the Tp1 and Tp2 genes from field isolates of T. parva has demonstrated polymorphism in both Ags, including the epitopes analyzed in the current study. We had previously reported differential recognition of one Tp1 allelic variant and two Tp2 variants by CD8 + T cell clones specific for the respective dominant epitopes (33). The availability of a large panel of NV of the Tp2 [49][50][51][52][53][54][55][56][57][58][59] epitope, together with specific T cell clones of defined TRB clonotypes, provided an opportunity to investigate the basis of escape from immune recognition of this epitope by the specific cell response.…”

Importância da resposta aos epítopos subdominantes, da proliferação e da recirculação de linfócitos T CD8+ durante a vacinação experimental contra a infecção pelo Trypanosoma cruzi.

“…Finally, our observations may have important implications regarding the basis for the strong immunodominance pattern observed after experimental infection with other intracellular parasites such as Plasmodium, Toxoplasma gondii and Theileria parva [50,51,[54][55][56][57].…”

“…Os epítopos imunodominantes variam de acordo com as cepas de T. cruzi de tal forma que um epítopo pode ser imunodominante na infecção com uma cepa e subdominante na infecção com outra cepa em hospedeiros geneticamente idênticos (52,55). cruzi (37,57). A imunidade mediada por estes linfócitos é dependente de IFN-γ e perforina já que camundongos geneticamente modificados que não expressam estas moléculas são incapazes de desenvolver imunidade protetora (37).…”