Disease relevance of H2-Q9

• Using an MHC class I-deficient melanoma as a model tumor, we demonstrate that Q9, a murine MHC class Ib molecule from the Qa-2 family, expressed on the surface of tumor cells, protects syngeneic hosts from melanoma outgrowth [1].
• By Northern hybridization, polymerase chain reaction (PCR) studies on cDNA, Southern hybridization, Western blotting, and nucleotide sequence analysis, the Q5k gene was identified as the gene encoding the Qa-2k antigen expressed on BW5147 lymphoma cells derived from a mouse of AKR strain (H-2k, Qa-2-) [2].
• We now find that by this definition classical class I MHC molecules, H-2Db, are concentrated in domains in the membranes of K78-2 hepatoma cells, while the nonclassical class I-related molecules, Qa-2, are free to pass the boundaries of these domains [3].
• A total of 18 Ped-2B2-reactive Pediococcus spp. isolates were isolated from eight food samples and assayed for bacteriocin production [4].

High impact information on H2-Q9

• A glycophospholipid anchor is required for Qa-2-mediated T cell activation [5].
• Our studies show that only lymphocytes from transgenic mice carrying GPI-anchored forms of Qa-2 can be activated in vitro by Qa-2-specific antibodies [5].
• Proteins associated with beta 2-microglobulin in the mouse include the classical transplantation antigens (H-2K, D and L), the thymus leukaemia antigen (TL) and certain haematopoietic cell differentiation antigens (Qa-1 and Qa-2) [6].
• Four highly homologous cell surface proteins, K, D, L, and Qa-2 (refs 1-4), belonging to this multigene family have been analysed [7].
• Qa-2 is a nonclassical class I molecule encoded by the Q7 gene within the mouse major histocompatibility complex (MHC) [8].

Biological context of H2-Q9

• These results show that both the Q7 and Q9 genes encode the mouse Ped phenotype [9].
• The protein product of the Ped gene, the Qa-2 protein, is a major histocompatibility complex (MHC) class Ib protein [9].
• The Ped (preimplantation embryonic development) gene influences the rate of preimplantation embryonic development and subsequent embryonic survival [9].
• Both the probe for Tcp-1 and that for Qa-2, 3 hybridized to clearly different positions on t and non-t chromosomes, thus making visible the extent of the two inversions [10].
• We also analysed the Ped gene expression pattern, both at the mRNA and at the protein level, in these lineages [11].

Anatomical context of H2-Q9

• In this study, we determined whether the Ped fast phenotype of blastocysts is due to an increased number of blastomeres in the trophectoderm (TE), the inner cell mass (ICM), or both [11].
• While soluble variants of Qa-2 have been previously detected in T lymphocytes, we now demonstrate the presence of mRNA for one of the two known soluble forms of Qa-2 in eight-cell embryos and in blastocysts [12].
• Qa-2 is glycosylphosphatidylinositol (GPI) linked in the cell membrane [13].
• METHOD OF STUDY: Incorporation of Qa-2 into the membranes of T cells and embryos was measured by FACScan and Immuno-PCR, respectively [14].
• These results revealed that the Qa-2k antigen was distinct from the normal Qa-2 antigen expressed on H-2b lymphocytes although it cross-reacted with some Qa-2-specific mAbs [2].

Associations of H2-Q9 with chemical compounds

• In this report, we address the biochemical relationships among Qa-2, Qa-6, and the 20-8-4 cross-reactive molecule by using immunoprecipitation and polyacrylamide gel electrophoresis [15].
• As a result, Qa-2 proteins cluster in cholesterol- and sphingolipid-rich lipid raft microdomains in the cell membrane and can signal via raft-associated intracellular signaling molecules [13].
• Qa-2-dependent selection of CD8alpha/alpha T cell receptor alpha/beta(+) cells in murine intestinal intraepithelial lymphocytes [16].
• Comparative mapping of the arginine-labeled tryptic peptides from Qa-2, H-2Kb, and H-2Db molecules indicate that Qa-2 is structurally distinct but that there is considerable structural homology; 21-43% of the Qa-2 peptides co-chromatograph with peptides derived from H-2Db and H-2Kb, respectively [17].
• A 12-hr TM treatment did not significantly alter the levels of H-2Kb, Db, or Qa-2; however, such treatment decreased the surface expression of the Qa-1b allelic product to undetectable levels [18].

Other interactions of H2-Q9

• The Qed-1 locus was mapped distal to Qa-2 [19].

Analytical, diagnostic and therapeutic context of H2-Q9

• We performed reverse transcription-polymerase chain reaction (PCR) and Immuno-PCR and found that the Ped gene is expressed at the mRNA and protein level in whole embryos and in isolated ICM cells [11].
• By taking advantage of the selective association of beta2mu with H-2, Qa-2, and TL antigens, and by using the technique of sequential immunoprecipitation, we demonstrated two previously undescribed guinea pig molecules reactive with anti-guinea pig beta2mu [20].
• To investigate further the features that signal cleavage and PI addition, we have studied mutants of two closely related murine class I MHC molecules: the PI-linked Ag, Q9b, from the Qa-2 Ag family, and the integral membrane transplantation antigen, H-2Ld [21].
• It is possible that the Qa-2 deletion polymorphism is segregating in the population, and a larger sample size would identify some Qa-2 negative mice [22].
• A highly sensitive enzyme-linked immunosorbent assay (ELISA) procedure was used to detect Qa-2 antigens on mouse embryos [23].

References