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
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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.
KeywordsTheileria parva CD8+ T cell epitopes Class I MHC Ankole cattle Pyrosequencing
We are grateful to Dr. Joerg Jores of ILRI for reviewing the manuscript. We also wish to thank Giles Prettejohn of the Ol Pejeta Conservancy in Kenya whose efforts were instrumental to the completion of this study. The study was funded by the DFG German-African Cooperation Projects in Infectiology: ‘Molecular epidemiology network for promotion and support of delivery of life vaccines against Theileria parva and Theileria annulata infection in Eastern and Northern Africa (SE 862/2-1)’. Some of the work described in this paper was also supported by the CGIAR Consortium research project CRP3.7.
- Graham SP, Pellé R, Honda Y, Mwangi DM, Tonukari NJ, Yamage M, Glew EJ, de Villiers EP, Shah T, Bishop R, Abuya E, Awino E, Gachanja J, Luyai AE, Mbwika F, Muthiani AM, Ndegwa DM, Njahira M, Nyanjui JK, Onono FO, Osaso J, Saya RM, Wildmann C, Fraser CM, Maudlin I, Gardner MJ, Morzaria SP, Loosmore S, Gilbert SC, Audonnet JC, van der Bruggen P, Nene V, Taracha EL (2006) Theileria parva candidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes. Proc Natl Acad Sci U S A 103(9):3286–3291CrossRefPubMedPubMedCentralGoogle Scholar
- Graham S, Honda Y, Pelle R, Mwangi DM, Glew EJ, DeVilliers EP, Shah T, Bishop R, van der Bruggen P, Nene V, Taracha ELN (2007) A novel strategy for the identification of antigens that are recognised by Bovine MHC class I restricted cytotoxic T cells in a protozoan infection using reverse vaccinology. Immunome Res 3:2CrossRefPubMedPubMedCentralGoogle Scholar
- Graham SP, Pellé R, Yamage M, Mwangi DM, Honda Y, Mwakubambanya RS, de Villiers EP, Abuya E, Awino E, Gachanja J, Mbwika F, Muthiani AM, Muriuki C, Nyanjui JK, Onono FO, Osaso J, Riitho V, Saya RM, Ellis SA, McKeever DJ, MacHugh ND, Gilbert SC, Audonnet JC, Morrison WI, van der Bruggen P, Taracha EL (2008) Characterization of the fine specificity of bovine CD8 T-cell responses to defined antigens from the protozoan parasite Theileria parva. Infect Immun 76(2):685–694CrossRefPubMedPubMedCentralGoogle Scholar
- Nielsen M, Lundegaard C, Blicher T, Lamberth K, Harndahl M, Justesen S, Røder G, Peters B, Sette A, Lund O, Buus S (2007) NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence. PLoS One 2(8):e796CrossRefPubMedPubMedCentralGoogle Scholar
- Norval RAI, Perry BD, Young AS (1992) The epidemiology of Theileria in Africa. Academic, LondonGoogle Scholar
- Obara I, Ulrike S, Musoke T, Spooner PR, Jabbar A, Odongo D, Kemp S, Silva JC, Bishop RP (2015) Molecular evolution of a central region containing B cell epitopes in the gene encoding the p67 sporozoite antigen within a field population of Theileria parva. Parasitol Res 114(5):1729–1737CrossRefPubMedPubMedCentralGoogle Scholar
- Pandya M, Rasmussen M, Hansen A, Nielsen M, Buus S, Golde W, Barlow J (2015) A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules. Immunogenetics 67(11):691–703Google Scholar
- Swofford DL (2002) PAUP: phylogenetic analysis using parsimony and other methods. Version 4. Sinauer Associates, SunderlandGoogle Scholar