title: Sequence diversity between class I MHC loci of African native and introduced Bos taurus cattle in Theileria parva endemic regions: in silico peptide binding prediction identifies distinct functional clusters.
abstract: There is strong evidence that the immunity induced by live vaccination for control of the protozoan parasite Theileria parva is mediated by class I MHC-restricted CD8(+) T cells directed against the schizont stage of the parasite that infects bovine lymphocytes. The functional competency of class I MHC genes is dependent on the presence of codons specifying certain critical amino acid residues that line the peptide binding groove. Compared with European Bos taurus in which class I MHC allelic polymorphisms have been examined extensively, published data on class I MHC transcripts in African taurines in T. parva endemic areas is very limited. We utilized the multiplexing capabilities of 454 pyrosequencing to make an initial assessment of class I MHC allelic diversity in a population of Ankole cattle. We also typed a population of exotic Holstein cattle from an African ranch for class I MHC and investigated the extent, if any, that their peptide-binding motifs overlapped with those of Ankole cattle. We report the identification of 18 novel allelic sequences in Ankole cattle and provide evidence of positive selection for sequence diversity, including in residues that predominantly interact with peptides. In silico functional analysis resulted in peptide binding specificities that were largely distinct between the two breeds. We also demonstrate that CD8(+) T cells derived from Ankole cattle that are seropositive for T. parva do not recognize vaccine candidate antigens originally identified in Holstein and Boran (Bos indicus) cattle breeds.
authors: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163, Berlin, Germany. iobara@zedat.fu-berlin.de.
authors: Isaiah
authors: I
authors: Obara
authors: Center for Biological Sequence Analysis (CBS), Department of Systems Biology, The Technical University of Denmark, Building 208, DK-2800, Lyngby, Denmark.|Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, B 1650 HMP, Buenos Aires, Argentina.
authors: Morten
authors: M
authors: Nielsen
authors: Berlin Center for Genomics in Biodiversity Research (BeGenDiv), Königin-Luise-Str. 6-8, 14195, Berlin, Germany.
authors: Marie
authors: M
authors: Jeschek
authors: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163, Berlin, Germany.
authors: Ard
authors: A
authors: Nijhof
authors: Berlin Center for Genomics in Biodiversity Research (BeGenDiv), Königin-Luise-Str. 6-8, 14195, Berlin, Germany.|Leibniz-Institute for Zoo and Wildlife Research (IZW), Evolutionary Genetics, Alfred- Kowalke-Straße 17, D-10315, Berlin, Germany.
authors: Camila J
authors: CJ
authors: Mazzoni
authors: International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi, 00100, Kenya.
authors: Nicholas
authors: N
authors: Svitek
authors: International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi, 00100, Kenya.
authors: Lucilla
authors: L
authors: Steinaa
authors: International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi, 00100, Kenya.
authors: Elias
authors: E
authors: Awino
authors: International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi, 00100, Kenya.
authors: Cassandra
authors: C
authors: Olds
authors: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163, Berlin, Germany.
authors: Ahmed
authors: A
authors: Jabbar
authors: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163, Berlin, Germany.
authors: Peter-Henning
authors: PH
authors: Clausen
authors: International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi, 00100, Kenya.
authors: Richard P
authors: RP
authors: Bishop
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000469:parasitology*; D002417:Cattle; D003198:Computer Simulation; D019353:Endemic Diseases; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005805:Genes, MHC Class I / Q000235:genetics* / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012984:Software; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D016797:Theileria parva / Q000235:genetics* / Q000276:immunology; D013801:Theileriasis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology
chemical_list: D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments
keywords: Ankole cattle; CD8+ T cell epitopes; Class I MHC; Pyrosequencing; Theileria parva