Peptide motifs of the single dominantly expressed class I molecule explain the striking MHC-determined response to Rous sarcoma virus in chickens

Abstract

Compared with the MHC of typical mammals, the chicken MHC is smaller and simpler, with only two class I genes found in the B12 haplotype. We make five points to show that there is a singledominantly expressed class I molecule that can have a strong effect on MHC function. First, we find only one cDNA for two MHC haplotypes (B14 and B15) and cDNAs corresponding to two genes for the other six (B2, B4, B6, B12, B19, and B21). Second, we find, for the B4, B12, and B15 haplotypes, that one cDNA is at least 10-fold more abundant than the other. Third, we use 2D gel electrophoresis of class I molecules from pulse-labeled cells to show that there is only one heavy chain spot for the B4 and B15 haplotypes, and one major spot for the B12 haplotype. Fourth, we determine the peptide motifs for B4, B12, and B15 cells in detail, including pool sequences and individual peptides, and show that the motifs are consistent with the peptides binding to models of the class I molecule encoded by the abundant cDNA. Finally, having shown for three haplotypes that there is a single dominantly expressed class I molecule at the level of RNA, protein, and antigenic peptide, we show that the motifs can explain the striking MHC-determined resistance and susceptibility to Rous sarcoma virus. These results are consistent with the concept of a ''minimal essential MHC'' for chickens, in strong contrast to typical mammals.antigen presentation ͉ avian ͉ essential ͉ evolution ͉ minimal

Extensive Allelic Diversity of MHC Class I in Wild Mallard Ducks

“…Notably, polymorphism in a1 has a greater influence on peptide specificity (57). Although nothing is known about the peptides that are bound by these clefts, duck alleles have critical residues in common with the peptide-binding clefts of the chicken (22). However, no allele has a cleft with positive charges identical to the B4 allele at BF2 (22).…”

“…Although nothing is known about the peptides that are bound by these clefts, duck alleles have critical residues in common with the peptide-binding clefts of the chicken (22). However, no allele has a cleft with positive charges identical to the B4 allele at BF2 (22). An examination of the polymorphic residues among the alleles of the UAA locus show they differ in the residues that line the pockets of the peptide-binding clefts, thus generating alleles with different functional specificity.…”

“…Overall, the MHC class I alleles show great di-U*06-09 (AY841881-4), U*10-15 (AB115241-6), and chicken BF2 B12 (Z54326), and accession numbers for wild mallard alleles U*16-76 are listed in Materials and Methods. Polymorphic residues implicated in function were deduced from structural studies of human MHC alleles (50) and comparison with chicken alleles (22). versity, and wild and domestic mallard alleles do not segregate independently.…”

“…In the chicken, the transporters for Ag processing (TAPs) can transport best the peptides that will fit the allele at the adjacent BF2 locus (21). The genes at BF1 show limited polymorphism and are expressed at one-tenth the level of BF2 (22).…”

No evidence for immunoproteasomes in chicken lymphoid organs and activated lymphocytes

“…β1i favors cleavage after hydrophobic residues instead of acidic ones. Further, peptides generated by the proteasome are presented on MHC class I molecules but those originating from the immunoproteasome contain more suitable MHC class I ligands in mice and humans, because the binding groove has a higher binding affinity for peptides with hydrophobic or basic C-termini (Kaufman et al 1995;Koch et al 2007;Wallny et al 2006). In this context, another type of proteasome should be mentioned, the thymoproteasome, which is characterized by the catalytic proteins β1i and β2i as well as β5t and is unique to cortical thymic epithelial cells (cTECs) residing in the cortex of the thymus.…”