Article

BG1 has a major role in MHC-linked resistance to malignant lymphoma in the chicken

Department of Molecular Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 09/2009; 106(39):16740-5. DOI: 10.1073/pnas.0906776106
Source: PubMed

ABSTRACT Pathogen selection is postulated to drive MHC allelic diversity at loci for antigen presentation. However, readily apparent MHC infectious disease associations are rare in most species. The strong link between MHC-B haplotype and the occurrence of virally induced tumors in the chicken provides a means for defining the relationship between pathogen selection and MHC polymorphism. Here, we verified a significant difference in resistance to gallid herpesvirus-2 (GaHV-2)-induced lymphomas (Marek's disease) conferred by two closely-related recombinant MHC-B haplotypes. We mapped the crossover breakpoints that distinguish these haplotypes to the highly polymorphic BG1 locus. BG1 encodes an Ig-superfamily type I transmembrane receptor-like protein that contains an immunoreceptor tyrosine-based inhibition motif (ITIM), which undergoes phosphorylation and is recognized by Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2). The recombinant haplotypes are identical, except for differences within the BG1 3'-untranslated region (3'-UTR). The 3'-UTR of the BG1 allele associated with increased lymphoma contains a 225-bp insert of retroviral origin and showed greater inhibition of luciferase reporter gene translation compared to the other allele. These findings suggest that BG1 could affect the outcome of GaHV-2 infection through modulation of the lymphoid cell responsiveness to infection, a condition that is critical for GaHV-2 replication and in which the MHC-B haplotype has been previously implicated. This work provides a mechanism by which MHC-B region genetics contributes to the incidence of GaHV-2-induced malignant lymphoma in the chicken and invites consideration of the possibility that similar mechanisms might affect the incidence of lymphomas associated with other oncogenic viral infections.

0 Followers
 · 
140 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Major histocompatibility complex (MHC) is a highly polymorphic gene and plays an important role in immune system for vertebrate. To understand the polymorphism character of domestic, we cloned 32 cDNAs of MHC class I α genes of two local chicken breeds in different areas of China. There were 112 variable amino acid residues in all five domains (leader peptide, α1, α2, α3 and TM/CY domains) of the putative α chain, and 76 of them were located in α1 and α2 domains. There were 23 to 25 polymorphic sites with high mutation frequency in α1 and α2 domains. Comparison of chicken with duck, human and mouse revealed that the two domains were highly similar among different species, and some highly polymorphic sites were located at the sites 9, 111(114), 113 (116) and 153 (156). Analysis of the phylogenetic tree indicated no relationship between the breeds and polymorphic alleles. All these results therefore indicate that MHC I class molecule of domestic chickens was more influenced by the pressure of common pathogens rather than geographic differences.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Turkeys are extremely sensitive to aflatoxin B1 (AFB1) which cause decreased growth, immunosuppression and liver necrosis. The purpose of this study was to determine whether probiotic Lactobacillus, shown to be protective in animal and clinical studies, would likewise confer protection in turkeys, which were treated for 11 days with either AFB1 (AFB; 1 ppm in diet), probiotic (PB; 1 X 1011 CFU/ml; oral, daily), probiotic + AFB1 (PBAFB), and PBS control (CNTL). The AFB1 induced drop in body and liver weights were restored to normal in CNTL and PBAFB groups. Hepatotoxicity markers were not significantly reduced by probiotic treatment. Major histocompatibility complex (MHC) genes BG1 and BG4, which are differentially expressed in liver and spleens, were not significantly affected by treatments. These data indicate modest protection, but the relatively high dietary AFB1 treatment, and the extreme sensitivity of this species may reveal limits of probiotic-based protection strategies.
    Research in Veterinary Science 10/2014; DOI:10.1016/j.rvsc.2014.06.008 · 1.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The major histocompatibility complex (MHC) of proteins that exists in all vertebrates is encoded by a cluster of genes associated with the immune response and related functions. MHC is divided into MHC I, II, and III; MHC I is involved in antigenic presentation, binding T cell receptors, and leading ultimately to specific cellular immune responses. The complicated functions of MHC I are determined by the nature of the complex. The crystal structure of MHC I has been solved for many animals, revealing the relationship between spatial structure and function. MHC I consists of an α heavy chain and a β2m light chain, both ligated non-covalently to a complex when a peptide is bound to the antigenic-binding groove. The α heavy chain is divided into an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain consists of sub-regions α1, α2, and α3. The α1 and α2 together form the antigenic-binding groove and bind antigenic peptides with 8–10 amino acid residues. MHC I can form a stable spatial structure; however, it should be noted that there are differences in the structure of MHC I among animal species, including anchored amino acids in binding peptides, binding sites, molecular distance, crystallization conditions, etc. Here, progress in determination of the crystal structure of human, mouse, chicken, non-human primate, and swine MHC I is described in detail.
    Chinese Science Bulletin 04/2014; 59(12):1308-1316. DOI:10.1007/s11434-014-0211-z · 1.37 Impact Factor