Genetic variation at the MHC in a population of introduced wild turkeys.

Genetic variation in the major histocompatibility complex (MHC) is known to affect disease resistance in many species. Investigations of MHC diversity in populations of wild species have focused on the antigen presenting class IIß molecules due to the known polymorphic nature of these genes and the role these molecules play in pathogen recognition. Studies of MHC haplotype variation in the turkey ( Meleagris gallopavo ) are limited. This study was designed to examine MHC diversity in a group of Eastern wild turkeys ( Meleagris gallopavo silvestris ) collected during population expansion following reintroduction of the species in southern Wisconsin, USA. Southern blotting with BG and class IIß probes and single nucleotide polymorphism (SNP) genotyping was used to measure MHC variation. SNP analysis focused on single copy MHC genes flanking the highly polymorphic class IIß genes. Southern blotting identified 27 class IIß phenotypes, whereas SNP analysis identified 13 SNP haplotypes occurring in 28 combined genotypes. Results show that genetic diversity estimates based on RFLP (Southern blot) analysis underestimate the level of variation detected by SNP analysis. Sequence analysis of the mitochondrial D-loop identified 7 mitochondrial haplotypes (mitotypes) in the sampled birds. Results show that wild turkeys located in southern Wisconsin have a genetically diverse MHC and originate from several maternal lineages.

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

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.

Extended gene map reveals tripartite motif, C-type lectin, and Ig superfamily type genes within a subregion of the chicken MHC-B affecting infectious disease.

MHC haplotypes have a remarkable influence on whether tumors form following infection of chickens with oncogenic Marek's disease herpesvirus. Although resistance to tumor formation has been mapped to a subregion of the chicken MHC-B region, the gene or genes responsible have not been identified. A full gene map of the subregion has been lacking. We have expanded the MHC-B region gene map beyond the 92-kb core previously reported for another haplotype revealing the presence of 46 genes within 242 kb in the Red Jungle Fowl haplotype. Even though MHC-B is structured differently, many of the newly revealed genes are related to loci typical of the MHC in other species. Other MHC-B loci are homologs of genes found within MHC paralogous regions (regions thought to be derived from ancient duplications of a primordial immune defense complex where genes have undergone differential silencing over evolutionary time) on other chromosomes. Still others are similar to genes that define the NK complex in mammals. Many of the newly mapped genes display allelic variability and fall within the MHC-B subregion previously shown to affect the formation of Marek's disease tumors and hence are candidates for genes conferring resistance.

2004 Nomenclature for the chicken major histocompatibility (B and Y) complex.

The first standard nomenclature for the chicken (Gallus gallus) major histocompatibility (B) complex published in 1982 describing chicken major histocompatibility complex (MHC) variability is being revised to include subsequent findings. Considerable progress has been made in identifying the genes that define this polymorphic region. Allelic sequences for MHC genes are accumulating at an increasing rate without a standard system of nomenclature in place. The recommendations presented here were derived in workshops held during International Society of Animal Genetics and Avian Immunology Research Group meetings. A nomenclature for B and Y (Rfp-Y) loci and alleles has been developed that can be applied to existing and newly defined haplotypes including recombinants. A list of the current standard B haplotypes is provided with reference stock, allele designations, and GenBank numbers for corresponding MHC class I and class IIbeta sequences. An updated list of proposed names for B recombinant haplotypes is included, as well as a list of over 17 Y haplotypes designated to date.

Memory T cells protect chicks from acute infectious bronchitis virus infection.

Infectious bronchitis has remained one of the most difficult to control diseases in poultry since it was first described in 1931. Previous studies demonstrated that primary CD8(+) T lymphocytes collected at 10 days post-infection (p.i.) are important in controlling acute infection. To further investigate the role of memory T cells in protection, T lymphocytes collected from B19/B19 chicken spleens at 2, 3, 4, and 6 weeks p.i. were transferred to six-day-old syngeneic chicks one day prior to challenging with 10(6) EID(50) of the IBV Gray strain. Memory immune T cells collected at 3 to 6 weeks p.i. provided dose responsive protection from clinical illness. The greatest protection was observed after the transfer of 10(7) T cells collected at 6 weeks p.i., whereas T cells collected at 2 weeks p.i. did not protect. Annexin-V staining of the spleen cells demonstrated that the cells collected at 2 weeks p.i. were undergoing significantly more apoptosis than cells collected at 10 days p.i. Specific antibody production in sera collected at 7 days p.i. did not correlate with protection. T cell subtype depletion demonstrated that CD8(+), not CD4(+), T cells were critical. Memory T cells can be detected in peripheral blood mononuclear cells up to at least 10 weeks p.i. These results demonstrated that IBV specific CD8(+) memory T cells generated at 3 to 6 weeks p.i. can protect syngeneic chicks from acute IBV infection.

Alloantigen system L affects the outcome of rous sarcomas.

This study was designed to examine the alloantigen system L effects on Rous sarcomas in three B complex genotypes. The parental stock was 50% Modified Wisconsin Line 3 x White Leghorn Line NIU 4 and 50% inbred Line 6.15-5. Pedigree matings of two B(2)B(5) L(1)L(2) sires to five B(2)B(5) L(1)L(2) dams per sire produced experimental chicks segregating for B and L genotypes. Chicks were inoculated with 20 pock-forming units (pfu) of Rous sarcoma virus (RSV) at 6 weeks of age. Tumors were scored six times over 10 weeks postinoculation after which the tumor scores were used to assign a tumor profile index (TPI) to each chicken. Tumor growth over time and TPI were evaluated by repeated-measures analysis of variance and analysis of variance, respectively. Six trials were conducted with a total of 151 chickens. The major histocompatibility (B) complex affected the responses as the B(2)B(2) and B(2)B(5) genotypes had significantly lower tumor growth over time and TPI than the B(5)B(5) genotype. Separate analyses revealed no significant L system effect in B(2)B(2) or B(2)B(5) backgrounds. However, L genotype significantly affected (P < 0.05) both tumor growth over time and TPI in B(5)B(5) chickens. B(5)B(5) L(1)L(2) birds had TPI significantly lower than B(5)B(5) L(1)L(1) chickens but not B(5)B(5) L(2)L(2). Mortality was lower in the B(5)B(5) L(1)L(2) birds than in B(5)B(5) L(2)L(2) chickens. The L system, or one closely linked, affects the growth and ultimate outcome of Rous sarcomas. The response may depend upon the genetic background as well as MHC type.