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Title: Association of the bovine leukocyte antigen major histocompatibility complex class II DRB3*4401 allele with host resistance to the Lone Star Tick, Amblyomma americanum

Author
item Olafson, Pia
item Pruett Jr, John
item STEELMAN, C - U ARKANSAS, FAYETTEVILLE

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2006
Publication Date: 4/10/2007
Citation: Olafson, P.U., Pruett Jr, J.H., Steelman, C.D. 2007. Association of the bovine leukocyte antigen major histocompatibility complex class II DRB3*4401 allele with host resistance to the Lone Star Tick, Amblyomma americanum. Veterinary Parasitology. 145(1-2):190-195.

Interpretive Summary: Ticks and tick-borne diseases are of veterinary, medical, and economic importance worldwide. While acaricide treatment has historically been effective at controlling tick populations, the development of resistance to these chemicals has prompted the investigation of alternative methods for control. Natural host resistance to tick infestation, which is believed to be heritable, has been well documented in the literature; however, the host genes that may play a role in the manifestation of tick resistance have yet to be identified. At our laboratory, we have established a herd of cattle that have been phenotyped for susceptibility to the horn fly and the Lone Star tick in an effort to identify genes that may contribute to natural host resistance. The major histocompatibility complex of cattle, known as the bovine leukocyte antigen (BoLA) complex, plays an integral role in disease and parasite susceptibility, and immune responsiveness of the host. Because of its importance at the host-tick interface, we analyzed DNA markers within the BoLA complex and sequenced the highly variable region of a BoLA gene (DRB3) from calves in the herd to evaluate whether the markers may be diagnostic for tick-resistance/-susceptibility. Interestingly, a DNA sequence variant of DRB3 was identified that associates with the tick-resistance phenotype. The identification of such markers potentially provides an avenue for improved breeding schemes for parasite resistance, which will be beneficial to the cattle industry.

Technical Abstract: The MHC of cattle, known as the bovine leukocyte antigen (BoLA) complex, plays an integral role in disease and parasite susceptibility, and immune responsiveness of the host. While susceptibility to tick infestation in cattle is believed to be heritable, genes that may be responsible for the manifestation of this phenotype remain elusive. In an effort to analyze the role that genes within the BoLA complex may play in host resistance to ticks, we have evaluated components of this sytem within a herd of cattle established at our laboratory that has been phenotyped for ectoparasite susceptibility. Of three microsatellite loci within the BoLA complex analyzed, alleles of two microsatellite loci within the BoLA class IIa cluster (DRB1-118 and DRB3-174) associated with the tick-resistant phenotype, prompting further investigation of gene sequences within this region, namely DRB3. DRB3 is a class IIa gene that encodes the ' chain of the DR class II BoLA molecule, the second exon of which is highly polymorphic since it encodes the antigen recognition site of the DR class II molecule. Analysis of the second exon of the DRB3 gene from the phenotyped calves in our herd revealed a significant association between the DRB3*4401 allele and the tick-resistant phenotype. Further, specific amino acid residues within the antigen recognition site encoded by DRB3 alleles in our herd were identified as putative tick-susceptible/-resistant motifs for the DR class II molecule. To our knowledge, this is the first report of a putative association between a class IIa sequence and tick-resistance. Elucidation of the mechanism involved in tick resistance will contribute to improving breeding schemes for parasite resistance, which will be beneficial to the cattle industry.