|TRUONG, ANH DUC - Chung-Ang University|
|BAN, JIHY - Chung-Ang University|
|PARK, BOYEONG - Chung-Ang University|
|HONG, YEONG HO - Chung-Ang University|
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2016
Publication Date: 7/1/2016
Publication URL: http://handle.nal.usda.gov/10113/5399132
Citation: Truong, A., Ban, J., Park, B., Hong, Y., Lillehoj, H.S. 2016. Characterization and functional analyses of a novel chicken CD8a variant X1 (CD8a1). Veterinary Immunology and Immunopathology. 94(7):2737-2751. doi: 10.2527/jas.2015-0133.
Interpretive Summary: Understanding the various receptor molecules that the host immune cells use to communicate with each other is critical to develop effective vaccines against pathogens. In this paper, ARS scientists collaborated with scientists at a South Korean university to study the nature of the molecular signaling which is induced by the Cell Surface Determinant 8 (CD8) receptor. CD8 receptor is present on a particular subset of host T lymphocytes which are important in host immune response to pathogens. These scientists demonstrated for the first time that different molecular structures of chicken CD8 molecule are being used to communicate with other cells of immune system. Understanding the molecular interactions among different components of the immune system will enable the development of effective vaccines against many infectious diseases.
Technical Abstract: We provide the first description of cloning, as well as structural and functional analysis of a novel variant in the chicken CD8alpha family, termed the CD8-alpha X1 (CD8alpha1) gene. Multiple alignment of CD8alpha1 with known CD8alpha and beta sequences of other species revealed relatively low conservation of amino acid residues involved in the specific and unique structural domains among CD8alphas. For example, cysteine residues that are involved in disulfide bonding to form the V domain are conserved. In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8alpha1 sequence, and the A beta-strand and complementarity-determining region (CDR) 1 and 2 sequences are poorly conserved between chicken CD8alpha1 and avian CD8alpha. Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. Moreover, the motif (CXCP) that is responsible for binding the p56 lymphocyte cell kinase subunit (p56lck) is missing in the CD8alpha1. The chicken CD8alpha1 genomic structure is similar to that of chicken CD8alpha, but their protein structures differ. Phylogenetic analysis showed that chicken CD8alpha1 grouped with known avian CD8alpha sequences, but was distantly related to the CD8alpha of other species. Moreover, we analyzed the signal transduction and cytokine response to CD8alpha1 treatment to determine the specific biological functions of chicken CD8alpha1 in immune cells. The results showed that chicken CD8alpha1 is a key regulator of transcription of the major histocompatibility complex class I and II promoter regions, and activates Janus kinase (JK), signal transducer and activator of transcription, and suppressor of cytokine signaling 1 signaling-related genes. Immune cells express functional CD8alpha1, which induces proinflammatory cytokines as well as innate immune responses. Therefore, our data indicate that CD8alpha1 may have immunoregulatory activity by regulating the expression of pro-inflammatory or anti-inflammatory cytokines via its effect on immune cells.