2011
DOI: 10.4049/jimmunol.1102009
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Escape from CD8+ T Cell Response by Natural Variants of an Immunodominant Epitope from Theileria parva Is Predominantly Due to Loss of TCR Recognition

Abstract: 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… Show more

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Cited by 20 publications
(30 citation statements)
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“…The disparity between the TRB chain repertoires of CD8 T cells specific for the two In a previous study, alanine scanning mutagenesis demonstrated that Lys 59 was the C-terminus anchor residue of the Tp2 49-59 epitope but an N-terminal anchor residue was not identified. 27 MHCCLUSTER 2.0 predictions indicating that a serine (Ser), alanine (Ala) or threonine (Thr) at P2 is the preferred N-anchor residue for 2*01201 28 suggests that single-alanine mutagenesis may not have affected MHC I binding either as a consequence of the similar biophysical characteristics of Ser and Ala (small and neutral) and/or the capacity of the tandem Ser 50 and Ser 51 residues to serve as alternative anchor residues. Further MHC I-binding competition assays using peptides in which either or both Ser 50 and Ser 51 residues of both the Tp2 49-59 ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…The disparity between the TRB chain repertoires of CD8 T cells specific for the two In a previous study, alanine scanning mutagenesis demonstrated that Lys 59 was the C-terminus anchor residue of the Tp2 49-59 epitope but an N-terminal anchor residue was not identified. 27 MHCCLUSTER 2.0 predictions indicating that a serine (Ser), alanine (Ala) or threonine (Thr) at P2 is the preferred N-anchor residue for 2*01201 28 suggests that single-alanine mutagenesis may not have affected MHC I binding either as a consequence of the similar biophysical characteristics of Ser and Ala (small and neutral) and/or the capacity of the tandem Ser 50 and Ser 51 residues to serve as alternative anchor residues. Further MHC I-binding competition assays using peptides in which either or both Ser 50 and Ser 51 residues of both the Tp2 49-59 ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…There is a self-similarity to these distributions that has led to our describing the repertoire as fractal (6). Such complex repertoires have also been observed in the mouse (7, 8) and cow (9). …”
Section: Introductionmentioning
confidence: 66%
“…Subsequent work demonstrated that these antigens are highly polymorphic and that the respective T‐cell responses are often parasite strain‐restricted. Elsewhere, we have discussed in further detail how this observed focusing of the CD8 T‐cell response on highly dominant polymorphic T‐cell epitopes is a key determinant of parasite strain specificity of CD8 T‐cell response . However, recent unpublished studies (H. Hemmink, W.I.…”
Section: Approaches To Development Of Subunit Vaccinesmentioning
confidence: 98%