The mouse major histocompatibility complex: some assembly required

Amadou, Claire; Kumánovics, Attila; Jones, Elsy P.; Lambracht-Washington, Doris; Yoshino, Masayasu; Lindahl, Kirsten Fischer

doi:10.1111/j.1600-065x.1999.tb01394.x

Cited by 59 publications

(58 citation statements)

References 105 publications

(68 reference statements)

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“…Engagement of NKG2D by MICA stimulates NK cells and some ␥͞␦ T cells and costimulates CD8 ϩ ␣͞␤ T cells (34)(35)(36). Interestingly, the mouse MHC does not contain class I-like genes thought to be orthologous to MICA or MICB (37). Indeed, among many members of the class I gene family, MICA and MICB are the only genes the rodent counterparts of which have not been identified (Fig.…”

Section: Discussionmentioning

confidence: 99%

A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex

Kasahara

Watanabe

Sumasu

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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A ll jawed vertebrates have two classes of structurally and functionally distinct major histocompatibility complex (MHC) molecules that present peptides to T cell receptors, thereby initiating an adaptive immune response (1). Class I molecules are integral membrane glycoproteins made up of a heavy chain and ␤ 2 -microglobulin that present peptides derived from intracellularly synthesized proteins to CD8 ϩ T cells (2). On the other hand, class II molecules, consisting of two integral membrane glycoproteins designated ␣ and ␤ chains, present peptides produced in or directed to the endosomal͞lysosomal compartment to CD4 ϩ T cells (3). In most animals including human and mouse, class I genes (the genes for the heavy chain of class I molecules) are tightly linked to class II genes (the genes for the ␣ and ␤ chains of class II molecules), collectively forming a gene cluster (1,4,5).Although class I genes that play a major role in antigen presentation map to the MHC, several class I-like genes located outside the MHC have been identified in human and mouse. Examples of such class I-like genes in mice include Cd1 (Cd1d1 and Cd1d2) (6, 7), Azgp1 (the gene for zinc-␣2-glycoprotein) (8, 9), Fcgrt (the gene for the heavy chain of the neonatal IgG Fc receptor) (10, 11), Procr (the gene for the endothelial protein C receptor) (12), H2ls (the gene for the H2 complex class 1-like polypeptide) (13,14), Hfe (the hemochromatosis gene) (15, 16), Raet1a-Raet1e (the genes for retinoic acid early transcripts 1␣-) (17, 18), and H60 (histocompatibility 60) (19). Although these genes have diverse functions, some unrelated to immunity, they all have structural similarities to MHC class I genes and thus qualify as members of the class I gene family.We describe here a family of mouse class I-like genes located outside the MHC. This gene family, which maps to the vicinity of the leukocyte receptor complex (LRC) on chromosome 7, has two members. Interestingly, the proteins encoded by this gene family are related most closely to the MICA͞MICB molecules encoded in the human MHC. After consultation with the International Committee on Standardized Genetic Nomenclature for Mice, we propose to call this newly discovered gene family Mill (MHC class I-like located near the LRC) and its two members Mill1 and Mill2. Materials and MethodsIsolation of Mill1 and Mill2 cDNA by RT-PCRs. A computer search of the mouse EST section of the GenBank database resulted in the identification of three clones predicted to encode two distinct, class I heavy chain-like molecules. Based on the sequences of these clones, we designed primers that enabled the isolation of full coding sequences of Mill1 and Mill2 cDNA. The primer sequences were 5Ј-TGGCTTGGGATCTTCAAAGT-3Ј (sense) and 5Ј-TCCTCTGTCTTGTTTGGCTGTT-3Ј (antisense) for Mill1 and 5Ј-TTTGCACAAAACTCCATTTGA-3Ј (sense) and 5Ј-AGAAACAGCCAAGCCTCAGTC-3Ј (antisense) for Mill2. The cDNA templates for PCR were synthesized as described (20) by using total cellular RNAs isolated from the skin of 1-day-old BALB͞cCrSlc mice (Mill1)...

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Section: Discussionmentioning

confidence: 99%

A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex

Kasahara

Watanabe

Sumasu

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…The H2-M region itself consists of class I-rich regions separated by clusters of nonclass I genes, termed framework genes (Amadou 1999;Amadou et al 1999). In the 790 kb of the H2-M region sequenced here, 18 previously characterized genes and pseudogenes were identified by similarity searches.…”

Section: Gene Organizationmentioning

confidence: 99%

“…Comparative physical mapping revealed extensive conservation of synteny within the Mhc, but in a patchwork pattern: so-called framework regions of near complete conservation of content and orientation of genes, mainly of nonimmune function, alternating with regions of species-specific expansion of rapidly evolving MHC class I and, to a lesser extent, class II genes (Amadou 1999;Amadou et al 1999). All mammals have one or more polymorphic MHC class Ia genes that function in classical antigen presentation.…”

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confidence: 99%

Species-Specific Class I Gene Expansions Formed the Telomeric 1 Mb of the Mouse Major Histocompatibility Complex

et al. 2003

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We have determined the complete sequence of 951,695 bp from the class I region of H2, the mouse major histocompatibility complex (Mhc) from strain 129/Sv (haplotype bc). The sequence contains 26 genes. The sequence spans from the last 50 kb of the H2-T region, including 2 class I genes and 3 class I pesudogenes, and includes the H2-M region up to Gabbr1. A 500-kb stretch of the H2-M region contains 9 class I genes and 4 pseudogenes, which fall into two subfamilies, M1 and M10, distinct from other mouse class I genes. This M1/M10 class I gene-cluster is separated from the centromeric H2-T and the telomeric H2-M4, -5 and -6 class I genes by "nonclass I genes". Comparison with the corresponding 853-kb region of the human Mhc, which includes the HLA-A region, shows a mosaic of conserved regions of orthologous nonclass I genes separated by regions of species-specific expansion of paralogous Mhc class I genes. The analysis of this mosaic structure illuminates the dynamic evolution of the Mhc class I region among mammals and provides evidence for the framework hypothesis.

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“…For example, comparison of the human and mouse MHC class I gene maps shows that there is an ancestral framework of non-MHC genes in which class I-like gene subregions are located. 3 These class I-encoding subregions then independently expanded in the two species. Independent post-speciation divergence of class I MHC during mammalian evolution may explain the differential usage of killer cell Ig-related receptor (KIR) vs Ly49 class I MHC receptors in primate and rodent natural killer (NK) cells, respectively.…”

Section: Introductionmentioning

confidence: 99%

Direct sequence comparison of two divergent class I MHC natural killer cell receptor haplotypes

Makrigiannis

Patel²,

Ml³

et al. 2005

Genes Immun

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The murine Ly49 gene family encoding natural killer cell receptors for class I MHC is an example of a rapidly evolving cluster of immune response genes. Determining the genomic sequence of the 129S6/SvEvTac (129S6) Ly49 cluster and comparing it to the known sequence of the C57BL/6 (B6) region provided insight into the mechanisms of Ly49 gene evolution. 129S6 contains 20 Ly49, many of which are pseudogenes and 40% of the genes have no counterpart in the B6 genome. The difference in gene content between these two strains is primarily the result of distinct patterns of gene duplication. Phylogenetic analyses of individual exons showed that Ly49 genes form distinct sub-families and an ancestral haplotype can be surmised. Dotplot analysis supports limited allelism in the two haplotypes; however, large regions of variation punctuate these islands of colinearity. These variable regions contain a high concentration of repetitive elements that are predicted to contribute to the dynamic evolution of this cluster. The extreme variation in Ly49 haplotype content between mouse strains provides a genetic explanation for the documented differences in natural killer cell phenotype, and also indicates that differences in natural killer cell function observed between B6 and 129-derived gene-targeted mice should be interpreted with caution.

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The mouse major histocompatibility complex: some assembly required

Cited by 59 publications

References 105 publications

A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex

A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex

Species-Specific Class I Gene Expansions Formed the Telomeric 1 Mb of the Mouse Major Histocompatibility Complex

Direct sequence comparison of two divergent class I MHC natural killer cell receptor haplotypes

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