Disease relevance of H2-Q7

• Correction of defects responsible for impaired Qa-2 class Ib MHC expression on melanoma cells protects mice from tumor growth [1].
• Q9-mediated protective immunity is lost or greatly diminished in mice deficient in CTL, including beta(2)-microglobulin knockout (KO), CD8 KO, and SCID mice [2].
• Similar analysis of thymoma cells transfected with cloned C57BL/10 genes showed that cell-surface Qa-2 molecules encoded by a Q7b cDNA and the Q7b or Q9b gene were sensitive to hydrolysis by PtdIns-PLC, whereas the H-2Kb and H-2Db gene products were resistant [3].
• In this study, we report that surface-expressed Q9 on 3LLA9F1 Lewis lung carcinoma and RMA T cell lymphoma also induces potent antitumor CTL responses [4].

High impact information on H2-Q7

• 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 [5].
• Our results suggest that the tissue-specific expression of Qa-2 may be controlled, in part, by mechanisms of alternate RNA splicing [6].
• In cultured cells the alternative splicing of the Qa-2 message is induced by T-cell activation splicing of the Qa-2 message is induced by T-cell activation with concanavalin A [7].
• While the H-2 antigens span the cell membrane, the Qa-2 molecules are attached to the cell surface via phospholipid anchors [7].
• In some cell lines almost all Qa-2 transcripts lack exon 5 [7].

Biological context of H2-Q7

• These results provide direct evidence that the Ped gene phenotype is at least partially encoded by the Q7/Q9 genes [8].
• Recent research in our laboratory has shown that the Ped phenotype is potentially encoded by the Q7 and/or Q9 gene because the Q7 and Q9 genes, but not the Q6 or Q8 gene, are expressed during preimplantation mouse embryonic development [9].
• In this study we utilized microinjection of transgenes to assess the functional roles of both the Q7 and Q9 genes in control of the rate of preimplantation development [9].
• This major histocompatibility complex (MHC) class I b protein is encoded by four genes, Q6, Q7, Q8, and Q9 [10].
• Likewise, all tested strains had a Q odd DNA sequence identical to Q7/Q9 in the B10 strain [11].

Anatomical context of H2-Q7

• It was found that all detectable Qa-2 antigen on the embryonic cell surface is sensitive to cleavage by PI-PLC and is therefore bound to the cell membrane by a GPI linkage [12].
• It was found that all four genes are transcribed in lymphocytes, but only Q7 and Q9 are transcribed in mouse embryos [10].
• Activated T cells transcribe an alternatively spliced mRNA encoding a soluble form of Qa-2 antigen [7].
• The canonical mRNA encoding the membrane form of Qa-2 predominates in unstimulated mouse tissues but the cultured cell lines, like activated T cells, express enhanced levels of the truncated mRNA [7].
• Both NK cells and CTLs appear to collaborate in restraining growth of Q9-positive tumors [1].

Associations of H2-Q7 with chemical compounds

• Furthermore, treatment of Qa-2 proteins from both sources with cyanogen bromide or alpha-chymotrypsin resulted in identical peptide fragmentation patterns [13].
• These results therefore provide a biochemical correlation between a cloned Qa-region gene produce expressed on the surface of transfected cells, and the Qa-2 glycoprotein on spleen cells that was described a decade ago by serologic methods [13].
• Susceptibility or resistance in BALB/c substrains may be associated to differences known to distinguish them, such as serum testosterone levels and Qa-2 protein expression [14].
• 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 [15].
• L1210 expresses classical H-2 class I molecules, and since it has been shown that DTIC treatment does not modify the expression of these molecules, this is a suitable model to study nonclassical class I antigens, such as Qa2 glycoproteins, and their potential role in tumorigenicity [16].

Regulatory relationships of H2-Q7

• Treatment of mouse preimplantation embryos with interferon gamma (gamma-IFN) did not induce expression of the Q6/Q8 genes but enhanced expression of the Q7/Q9 genes [17].

Other interactions of H2-Q7

• Thus, both Q7 and Q9 are candidates for the genes responsible for the Ped gene phenotype [10].
• We found that the microinjected individual Q7 and Q9 genes increased the rate of preimplantation development [9].
• Among the best characterized non-classical mouse major histocompatibility antigens are the Qa-2 molecules [7].
• Northern (RNA) blot hybridizations, polymerase chain reaction studies, and cDNA cloning experiments demonstrate that EC lines transcribe genes allelic to the Tla region gene "37", Qa-2 region gene "Q7", and another, previously uncharacterized, class I-like gene [18].
• Qa-region class I gene expression: identification of a second class I gene, Q9, encoding a Qa-2 polypeptide [19].

Analytical, diagnostic and therapeutic context of H2-Q7

• Microinjection of the Q7 and/or Q9 genes resulted in protein expression in 10-25% of the microinjected embryos [9].
• To confirm this apparent lack of genetic polymorphism, the polymerase chain reaction (PCR) technique was used to amplify a portion of the 3' end of the Q region genes, Q4 to Q9, from several independent wild-derived strains of mice [11].
• Therefore, in this study, the sensitivity of cell-surface Qa-2, H-2Kb, and H-2Db to hydrolysis by PtdIns-PLC was investigated biochemically by immunoprecipitation of radioiodinated molecules from cell lysates or supernatants [3].
• After treatment with endoglycosidase F, the Qa-2 polypeptide chains derived from C57BL/10 spleen and Q7b-transfected R1.1 cells displayed identical mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis because of removal of N-linked oligosaccharide residues [13].
• Using an enzyme-linked immunosorbent assay with an IgD-specific mAb and Qa-2-lacZ fusion protein, the existence of IgD in RS with specificity for Qa-2 was confirmed [20].

References