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Escape from CD8<sup>+</sup> T cell response by natural variants of an immunodominant epitope from <i>Theileria parva</i> is predominantly due to loss of TCR recognition

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  • Biology


Polymorphism of immunodominant CD8+ T cell epitopes can facilitate escape from immune recognition of pathogens, leading to strain-specific immunity. In this study, we examined the TCR β-chain (TRB) diversity of the CD8+ T cell responses of cattle against two immunodominant epitopes from Theileria parva (Tp1214-224 and Tp249-59) and investigated the role of TCR recognition and MHC binding in determining differential recognition of a series of natural variants of the highly polymorphic Tp249-59 epitope by CD8+ T cell clones of defined TRB genotype. Our results show that both TP1214-224 and Tp2(9-59 elicited CD8+ T cell responses using diverse TRB repertoires that showed a high level of stability following repeated pathogenic challenge over a 3-y period. Analysis of single-alanine substituted versions of the Tp249-59 peptide demonstrated that Tp249-59-specific clonotypes had a broad range of fine specificities for the epitope. Despite this diversity, all natural variants exhibited partial or total escape from immune recognition, which was predominantly due to abrogation of TCR recognition, with mutation resulting in loss of the lysine residue at P8, playing a particularly dominant role in escape. The levels of heterozygosity in individual Tp249-59 residues correlated closely with loss of immune recognition, suggesting that immune selection has contributed to epitope polymorphism.

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