The Phylogenetic History of the MHC Class I Gene Families in Pig, Including a Fossil Gene Predating Mammalian Radiation

Renard, Christine; Chardon, Patrick; Vaiman, M.

doi:10.1007/s00239-003-2491-9

Cited by 24 publications

(15 citation statements)

References 29 publications

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“…In contrast, it is conceivable that NCR and NKG2D as well as their ligands have not been subjected to the pressure that caused the evolution of MHC genes and their receptors. The porcine NCR and NKG2D ligands are unknown; however, comparison of porcine and human genomic sequences suggests the presence of one ULBP gene and one MIC-A/MIC-B-like gene (MIC2) in the pig genome (40,41). NKG2D ligands are generally poorly expressed by normal cells but are up-regulated in transformed, infected, and stressed cells in both mice and humans (25).…”

Section: Discussionmentioning

confidence: 99%

Human NK Cytotoxicity against Porcine Cells Is Triggered by NKp44 and NKG2D

Forte

Lilienfeld

Baumann

et al. 2005

The Journal of Immunology

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Pig-to-human xenotransplantation has been proposed as a means to alleviate the shortage of human organs for transplantation, but cellular rejection remains a hurdle for successful xenograft survival. NK cells have been implicated in xenograft rejection and are tightly regulated by activating and inhibitory receptors recognizing ligands on potential target cells. The aim of the present study was to analyze the role of activating NK receptors including NKp30, NKp44, NKp46, and NKG2D in human xenogeneic NK cytotoxicity against porcine endothelial cells (pEC). 51Cr release and Ab blocking assays were performed using freshly isolated, IL-2-activated polyclonal NK cell populations as well as a panel of NK clones. Freshly isolated NK cells are NKp44 negative and lysed pEC exclusively in an NKG2D-dependent fashion. In contrast, the lysis of pEC mediated by activated human NK cells depended on both NKp44 and NKG2D, since a complete protection of pEC was achieved only by simultaneous blocking of these activating NK receptors. Using a panel of NK clones, a highly significant correlation between anti-pig NK cytotoxicity and NKp44 expression levels was revealed. Other triggering receptors such as NKp30 and NKp46 were not involved in xenogeneic NK cytotoxicity. Finally, Ab-dependent cell-mediated cytotoxicity of pEC mediated by human NK cells in the presence of xenoreactive Ab was not affected by blocking of activating NK receptors. In conclusion, strategies aimed to inhibit interactions between NKp44 and NKG2D on human NK cells and so far unknown ligands on pEC may prevent direct NK responses against xenografts but not xenogeneic Ab-dependent cell-mediated cytotoxicity.

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Section: Discussionmentioning

confidence: 99%

Human NK Cytotoxicity against Porcine Cells Is Triggered by NKp44 and NKG2D

Forte

Lilienfeld

Baumann

et al. 2005

The Journal of Immunology

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“…Four locus-specific sites for the SLA-3 alleles are found in exon 1 and exon 2 (Smith et al 2005b). Phylogenetic tree analyzes reveal that the SLA-1 and -2 genes were closer to each other than to the SLA-3 gene (Renard et al 2003;Ando et al 2004).…”

Section: Polymorphism Of the Sla Class I Genesmentioning

confidence: 93%

“… ‡ The SLA‐11 gene is non‐classical/classical MHC class I gene designated as a fossil gene (Renard et al . 2003).…”

Section: Overall Physical Mapmentioning

confidence: 99%

“…2005b). Phylogenetic tree analyzes reveal that the SLA‐1 and ‐2 genes were closer to each other than to the SLA‐3 gene (Renard et al . 2003; Ando et al .…”

Section: Polymorphism Of the Sla Genesmentioning

confidence: 99%

“…The entire class III region also represents a large frozen block that is completely conserved. Among the 61 (Renard et al 2003). §The sequences of the wDYA and wDYB genes appear to be characteristic of DY sequences (Renard et al 2006).…”

Section: A Conserved Framework Of Non-mhc Genesmentioning

confidence: 99%

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Gene organization and polymorphism of the swine major histocompatibility complex

Andõ

Chardon

2006

Animal Science Journal

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The recent availability of the full‐length sequence of one haplotype of the swine leukocyte antigen (SLA) complex, the swine major histocompatibility complex (MHC), and significant progress in the studies on gene expression and polymorphisms led to major advances in deciphering its role in resistance to diseases in animals. The present status of the genomic organization and polymorphism of the SLA complex is presented in this Review. Additionally, a comparative analysis with mammalian MHC has also been provided. The sequenced SLA‐H01 haplotype harbors 152 loci including genuine SLA genes, non‐MHC genes and pseudogenes. Although the numbers of expressed SLA genes could vary across haplotypes, three SLA class Ia, three SLA class Ib, four SLA class IIa and four SLA class IIb genes are currently expressed. Except for the class I genes, which have no clear orthologs, the gene organization of the loci was highly conserved between humans and pigs. Moreover, the human leukocyte antigen (HLA) complex lies on a single chromosomal segment, whereas a centromere at the class II and III junction splits the SLA complex into two segments, without disturbing gene organization or impeding functionality. Over 400 SLA class I and II allele sequences available in databases have been recently clustered and assigned to a specific SLA locus according to a newly defined nomenclature system.

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Genetic polymorphism of the swine major histocompatibility complex (SLA) class�I genes, SLA-1, -2 and -3

et al. 2003

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In order to identify and characterize genetic polymorphism of the swine major histocompatibility complex ( Mhc: SLA) class I genes, RT-PCR products of the second and third exons of the three SLA classical class I genes, SLA-1, SLA-2 and SLA-3 were subjected to nucleotide determination. These analyses allowed the identification of four, eight and seven alleles at the SLA-1, SLA-2 and SLA-3 loci, respectively, from three different breeds of miniature swine and one mixed breed. Among them, 12 alleles were novel. Construction of a phylogenetic tree using the nucleotide sequences of those 19 alleles indicated that the SLA-1 and -2 genes are more closely related to each other than to SLA-3. Selective forces operating at single amino acid sites of the SLA class I molecules were analyzed by the Adaptsite Package program. Ten positive selection sites were found at the putative antigen recognition sites (ARSs). Among the 14 positively selected sites observed in the human MHC ( HLA) classical class I molecules, eight corresponding positions in the SLA class I molecules were inferred as positively selected. On the other hand, four amino acids at the putative ARSs were identified as negatively selected in the SLA class I molecules. These results suggest that selective forces operating in the SLA class I molecules are almost similar to those of the HLA class I molecules, although several functional sites for antigen and cytotoxic T-lymphocyte recognition by the SLA class I molecules may be different from those of the HLA class I molecules.

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The Phylogenetic History of the MHC Class I Gene Families in Pig, Including a Fossil Gene Predating Mammalian Radiation

Cited by 24 publications

References 29 publications

Human NK Cytotoxicity against Porcine Cells Is Triggered by NKp44 and NKG2D

Human NK Cytotoxicity against Porcine Cells Is Triggered by NKp44 and NKG2D

Gene organization and polymorphism of the swine major histocompatibility complex

Genetic polymorphism of the swine major histocompatibility complex (SLA) class�I genes, SLA-1, -2 and -3

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