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The alpha chain gene of H-2O has an unexpected location in the major histocompatibility complex.

ABSTRACT: A previously unknown major histocompatibility complex class II molecule consisting of the beta chain encoded by the H-2Ob gene and an unknown alpha chain was recently described. We now report that the alpha chain occurs in two allelic forms distinguished by charge difference. Using inbred recombinant mouse strains we were able to map the H-2Oa gene to a location between the A.TL and B10.MBR recombination points. Cosmids covering this region were used to isolate the gene. Sequence analysis revealed that the H-2Oa gene is the murine equivalent of the human HLA-DNA gene. These results indicate that the human HLA-DNA gene, the existence of which has long been known, is indeed coding for DO alpha, the alpha chain pairing with DO beta.

SUBMITTER: Karlsson L

PROVIDER: S-EPMC2119318 | biostudies-other | 1992 Aug

REPOSITORIES: biostudies-other

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The alpha chain gene of H-2O has an unexpected location in the major histocompatibility complex.

Karlsson L L Peterson P A PA

The Journal of experimental medicine 19920801 2

A previously unknown major histocompatibility complex class II molecule consisting of the beta chain encoded by the H-2Ob gene and an unknown alpha chain was recently described. We now report that the alpha chain occurs in two allelic forms distinguished by charge difference. Using inbred recombinant mouse strains we were able to map the H-2Oa gene to a location between the A.TL and B10.MBR recombination points. Cosmids covering this region were used to isolate the gene. Sequence analysis reveal ...[more]

PMID: 1354242

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Project description:Due to its high polymorphism and importance for disease resistance, the major histocompatibility complex (MHC) has been an important focus of many vertebrate genome projects. Avian MHC organization is of particular interest because the chicken Gallus gallus, the avian species with the best characterized MHC, possesses a highly streamlined minimal essential MHC, which is linked to resistance against specific pathogens. It remains unclear the extent to which this organization describes the situation in other birds and whether it represents a derived or ancestral condition. The sequencing of the zebra finch Taeniopygia guttata genome, in combination with targeted bacterial artificial chromosome (BAC) sequencing, has allowed us to characterize an MHC from a highly divergent and diverse avian lineage, the passerines.The zebra finch MHC exhibits a complex structure and history involving gene duplication and fragmentation. The zebra finch MHC includes multiple Class I and Class II genes, some of which appear to be pseudogenes, and spans a much more extensive genomic region than the chicken MHC, as evidenced by the presence of MHC genes on each of seven BACs spanning 739 kb. Cytogenetic (FISH) evidence and the genome assembly itself place core MHC genes on as many as four chromosomes with TAP and Class I genes mapping to different chromosomes. MHC Class II regions are further characterized by high endogenous retroviral content. Lastly, we find strong evidence of selection acting on sites within passerine MHC Class I and Class II genes.The zebra finch MHC differs markedly from that of the chicken, the only other bird species with a complete genome sequence. The apparent lack of synteny between TAP and the expressed MHC Class I locus is in fact reminiscent of a pattern seen in some mammalian lineages and may represent convergent evolution. Our analyses of the zebra finch MHC suggest a complex history involving chromosomal fission, gene duplication and translocation in the history of the MHC in birds, and highlight striking differences in MHC structure and organization among avian lineages.

Project description:An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation. Humoral response to MICA antigens has repeatedly been associated with lower graft survival and an increased risk of acute and chronic rejection following kidney and liver transplantation with few studies showing conflicting results. Although there are clear indications of MICA antibodies being associated with adverse graft outcome, a definitive consensus on this relationship has not been arrived yet. Furthermore, only a few studies have dealt with the impact of MICA donor-specific antibodies as compared to those that are not donor specific on graft outcome. In addition to the membrane bound form, a soluble isoform of MICA (sMICA), which has the potential to engage the natural killer cell-activating receptor NKG2D resulting in endocytosis and degradation of receptor-ligand interaction complex leading to suppression of NKG2D-mediated host innate immunity, has been a subject of intense discussion. Most studies on sMICA have been directed toward understanding their influence on tumor growth, with limited literature focusing its role in transplant biology. Furthermore, a unique dimorphism (methionine to valine) at position 129 in the α2 domain categorizes MICA alleles into strong (MICA-129 met) and weak (MICA-129 val) binders of NKG2D receptor depending on whether they have methionine or valine at this position. Although the implications of MICA 129 dimorphism have been highlighted in hematopoietic stem cell transplantation, its role in solid organ transplantation is yet to be explored. This review summarizes the currently available information on MICA antibodies, soluble MICA, and MICA-129 dimorphism in a setting of solid organ transplantation.

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The alpha chain gene of H-2O has an unexpected location in the major histocompatibility complex.

Publications

The alpha chain gene of H-2O has an unexpected location in the major histocompatibility complex.

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