Role of the Chicken T Cell Receptor-Beta Repertoire in Genetic Resistance to Marek's Disease

Authors: Hearn, Cari; Cheng, Hans

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 11/26/2019
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Marek’s disease (MD) is a T cell lymphoproliferative disease of chickens induced by the Marek’s disease virus (MDV), an oncogenic alphaherpesvirus. MDV has repeatedly shown increased virulence in MD-vaccinated flocks, prompting continued efforts in improved vaccines and enhanced genetic resistance. Model pairs of genetically MD-resistant and susceptible chicken lines that are either MHC-matched or MHC-congenic has allowed the study of T cell receptor (TCR) repertoires associated with MDV infection. Chickens resistant to MD showed higher usage of Vbeta-1 TCRs than susceptible chickens, in both the CD8 and CD4 subsets in the MHC-matched model, and in the CD8 subset only in the MHC-congenic model; and Vbeta-1+ CD8 cells expanded during MDV infection. The TCR locus was found to be divergent between MD-resistant and susceptible chickens in the MHC-matched model, with MD-resistant chickens expressing a greater number of Vbeta-1 TCRs and an increased representation of Vbeta-1 CDR1 loops with an aromatic residue at position 45. TCR Vbeta-1 CDR1 usage in resistant x susceptible F1 birds indicated that the most commonly used CDR1 variant was present only in the susceptible line, suggesting that selection for resistance in the MHC-matched model has optimized the TCR repertoire away from dominant recognition of one of the B2 haplotype MHC molecules. Finally, TCR downregulation during MDV infection in the MHC-matched model was observed most strongly in the MD-susceptible line, and TCR downregulation due to viral reactivation in a tumor cell line could be demonstrated to be virus-specific and not due to apoptosis induction.