Using random forest to classify T-cell epitopes based on amino acid properties and molecular features

ABSTRACTAlthough 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 parasiteTheileria annulatainfects leukocytes and causes an acute, often fatal lymphoproliferative disease in cattle. Building on previous evidence of strain-restricted CD8 T cell responses toT. 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 ofT. annulatademonstrated 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.

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Detection of protein fold similarity based on correlation of amino acid properties

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.96.25.14318 ◽

1999 ◽

Vol 96 (25) ◽

pp. 14318-14323 ◽

Cited By ~ 23

Author(s):

I. V. Grigoriev ◽

S.-H. Kim

Keyword(s):

Amino Acid ◽

Protein Fold ◽

Acid Properties ◽

Amino Acid Properties

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Antibody VH domain sequence analysis by a bioinformatics approach based on electronic amino acid properties may help to predict paratop location

Immunology Letters ◽

10.1016/j.imlet.2021.11.003 ◽

2021 ◽

Author(s):

Tatjana Srdic Rajic ◽

Radmila Metlas

Keyword(s):

Amino Acid ◽

Sequence Analysis ◽

Acid Properties ◽

Domain Sequence ◽

Amino Acid Properties ◽

Vh Domain

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Thyrotropin-Receptor and Thyroid Peroxidase-Specific T Cell Clones and Their Cytokine Profile in Autoimmune Thyroid Disease1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.11.4336 ◽

1997 ◽

Vol 82 (11) ◽

pp. 3655-3663

Author(s):

Maria Elena Fisfalen ◽

Ellen M. Palmer ◽

Gijs A. van Seventer ◽

Keyoumars Soltani ◽

Yoshikuni Sawai ◽

...

Keyword(s):

Amino Acid ◽

T Cell ◽

Thyroid Tissue ◽

Cytokine Profile ◽

Thyroid Peroxidase ◽

Amino Acid Residues ◽

T Cell Epitopes ◽

T Cell Clones ◽

Cell Clones ◽

Ifn Γ

We studied the cytokine profile and the immune responses to thyroid antigens of specific T cell clones (TCC) isolated from patients with Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). Antigen-specific TCC were reactive to thyroid peroxidase (TPO), thyroglobulin (Tg) or human recombinant TSH-receptor extracellular domain (TSH-R), and/or their respective peptides. Of the 43 clones derived from HT patients, 65% were reactive to TPO, and 59% of the 32 clones derived from GD patients were reactive to TSH-R. TPO epitopes 100–119 and 625–644 were recognized by 75% of HT-derived clones, whereas TSH-R epitopes 158–176, 207–222, and 343–362/357–376 were recognized by 85% of GD-derived TCC. The TCC were classified according to their cytokine profile into T helper cell (Th)0 [secreting interleukin (IL)-4, IL-5, interferon (IFN)-γ], Th1 (secreting IFN-γ) and Th2 (secreting IL-4 and/or IL-5). Tumor necrosis factor-β and IL-10 were produced by all subsets. The specific TCC were predominantly Th1-like cells in HT, and were Th0- and Th1-like cells in GD. Fifty three percent of Th0 clones were derived from GD patients and were reactive to TSH-R, whereas 50% of Th1 clones were derived from HT patients and were reactive to TPO or Tg. Most Th2 clones (82%) were reactive to TPO and were established from peripheral blood. All these clones produced IL-5, and 64% produced IL-4 and IL-10. Interestingly, IFN-γ was highly produced by TPO- or Tg-specific clones established from HT thyroid tissue. These results confirm at the clonal level our previous studies regarding T cell epitopes on TPO and TSH-R molecules and support the concept that immunodominant T cell epitopes are located on amino acid residues 100–119 and 625–644 of TPO in HT and amino acid residues 158–176, 207–222 and 343–362/357–376 of TSH-R in GD. Our studies also demonstrate that thyroid-specific T cells can be classified into Th0, Th1, and Th2 subsets. TPO- or Tg-specific clones with Th1 phenotype appear to be involved in the pathogenesis of HT, mediating thyroid tissue destruction, whereas TSH-R clones with Th0 phenotype may induce thyroid-stimulating autoantibodies in GD.

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