H-2-like genes in the Tla region of mouse chromosome 17.
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Animals↗
Biomedical subjects
L Flaherty
Publications and source records attributed to L Flaherty.
Polymorphism of a Qa-1-associated antigen defined by cytotoxic T cells. I. Qed-1a and Qed-1d.
Tlad mice have a distinct Qed-1 allele, Qed-ld. Its product is detected by cytotoxic T cells raised in C57BL/6 (H-2b, Tlab) mice against cells from a new recombinant, B6-TL.123+ (H-2b, Tlad/b). Qed-1d is also found on cells from B10.M, A.CA and B10.STC90 mice. It cross-reacts weakly with Qed-1b (C57BL/6 x BALB/c)F1 anti-B10.A(5R) effectors discriminate Qed-1a and Qed-1d, while C3H/HeJ anti-B10.BR effectors cross-react extensively. CB6F1 anti-5R effector cells also discriminate between the Qed-1 antigens of B6-Tlaa (H-2b, Tlaa) and those of B10.BR and other H-2k, Tlaa strains.
Animals↗
The biochemical genetics of TL antigens on mouse thymocytes.
Molecules bearing thymus leukemia (TL) alloantigen were isolated by immunoprecipitation from detergent-solubilized thymocyte lysates. Antisera used included monoclonal antibodies (anti-TL.m1, anti-TL.m2, anti-TL.m3), monospecific anti-TL.5 alloantisera and multispecific anti-TL.1,2,3,5 antiserum. Apparently, each of these reagents immunoprecipitates the same single 45,000 molecular weight Tla gene product as shown by identity on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing and by sequential precipitation studies. Allelic TL molecules, coded by the Tlaa and Tlad genes, were shown to be distinguishable by SDS-PAGE, and tryptic peptide mapping experiments. Both allelic TL molecules could be isolated from thymocytes of (Tlaa x Tlad)F1 mice. These results suggest that, at least for the Tlaa-Tlad allelic differences, the polymorphism and antigenicity of TL is determined by variation in amino acid composition.
Animals↗
Syngeneic tumor immunizations produce Qa antibodies. Discovery of a new Qa antigen, Qa-6.
BALB/cBy (Qa-2-) mice injected with the syngeneic tumor, ORA I-a (Qa-2+), produced antibodies to Qa-2 and a newly discovered antigen, Qa-6. Specific antisera against Qa-6, in the presence of complement, lyses approximately 40% of lymph-node lymphocytes and splenocytes. Strain distribution analyses indicate that Qa-6 is specified by a gene within the TL subregion of the major histocompatibility complex. Thus, Qa-6 is the third member of the Qa/TL subset of cell surface antigens which is anomalously expressed on certain tumor cells. This finding suggests that the Qa and TL molecules may have a unique, functional role on the cell surface.
Animals↗
Qa-2 does not display structural genetic polymorphism detectable on isoelectric-focusing gels.
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Animals↗
Murine monoclonal antikidney autoantibodies. I. Anti-renal proximal tubular basement membrane autoantibodies.
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Animals↗
Supramolecular relationships of membrane antigens on the murine thymocyte.
The topographical relationships of Thy-1, Ly-1, Ly-2, and T200 were examined on the murine thymocyte. The inhibition of the binding of radiolabelled monoclonal antibody after incubation with unlabelled heterologous antibody was used as a measure of the proximity of the target antigens on the cell surface. On unfixed cells, prior incubation with anti-Thy-1.2 impeded the attachment of labelled anti-Ly-1, anti-Ly-2, and anti-T200. Anti-T200, but not anti-Ly-1, or anti-Ly-2, was capable of impeding the attachment of labelled anti-Thy-1.2 on unfixed cells. In general, gentle fixation with paraformaldehyde did not alter these inter-relationships. The possible functional contributions of such supramolecular relationships are discussed.
Animals↗
Repeated isolation of unique Qa2+ Ia+ clonally derived cell lines from Qa2- mice.
Qa2+ tumor cell lines were previously isolated from individual BALB/cBy (Qa2-) splenic lymphomas induced by murine sarcoma virus-murine leukemia virus-Moloney (MSV-MuLV-M). Two clonally derived cell lines, ORA I-a and Thorbly, and one noncloned cell line, BOMS, expressed Qa2, but neither Ly-1 nor Ly-2 were detected. In order to determine whether eight cloned and two noncloned tumor cell lines all represented a unique population of transformed cells, the presence of a series of surface differentiation antigens as studied. In addition to Qa2, each cell line examined expressed IAd, IEd, H-2Kd, H-2Dd, and receptors for C3b and the Fc portion of immunoglobulin (Ig). Neither Thy-1.2 nor Ig were detected on the cell surfaces, and cytoplasmic Ig was not precipitated from metabolically radiolabeled and detergent-solubilized cell extracts. However, monocyte specific alpha-napththyl acetate esterase-containing granules were present in all cell lines examined. Therefore, a unique Qa2+ monocytic cell is repeatedly isolated after chronic MSV-MuLV-M infection. Further analysis of these cells may provide insight into both the regulation of Qa2 expression and the interactions between monocytes and lymphocytes during leukemogenesis.
Animals↗
Qa-1 and Qa-2 expression on CFU-s.
Multipotential stem cells can be detected in bone marrow cells preparations by injecting these cells into syngeneic irradiated hosts. Colonies (CFU-s) are visible macroscopically on the spleen after 8 days. Pretreatment of A-Tlab (Qa-1.2) bone marrow with A-anti-A-Tlab serum (anti-Qa-1.2), in the presence of complement, reduced CFU-s by 80% whereas A-Tlab anti-A serum (anti-Qa-1.1) treatment had no effect. Pretreatment of A(Qa-1.1) bone marrow with A-Tlab anti-A serum reduced macroscopic splenic colonies by 78%. Similar results were obtained by using C57BL/6 (Qa-1.2) and B6-Tlaa (Qa-1.1) bone marrow. Thus, both Qa-1.1 and Qa-1.2 are expressed on CFU-s. Qa-2 expression on CFU-2 was examined in the same manner. B6.KI anti-B6 (anti-Qa-2,3) serum reduced CFU-s numbers by 87% on B6 (Qa-2,3+) while having little or no effect on B6.KI (Qa-2,3-). Treatment with D3.262, a monoclonal anti-Qa-2 antibody, reduced B6 CFU-s by 80%, and had no effect on B6.KI CFU-s. Detection of Qa-1 and Qa-2 on CFU-s underscores the wide distribution of the Qa antigens in the hematopoietic system.
Animals↗
Qa-2, H-2K, and H-2D alloantigens evolved from a common ancestral gene.
The Tla region located on the murine 17th chromosome controls several serologically defined cell surface antigens. These antigens, referred to as Qa-1-5 and TL, are expressed on a variety of hematopoeitic cell populations. In the present studies we have immunoprecipitated isotopically labeled Qa-2 and H-2 molecules from mitogen-stimulated B6 spleen cells. Sequential immunoprecipitation experiments have shown that the determinants recognized by alpha Qa-2, alpha H-2Kb, and alpha H-2Db alloantisera reside on separate molecular species. 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. Similar levels of homology are observed when Qa-2 is compared with H-2Kk or H-2Dd. The results show that the Qa-2 alloantigen is encoded by a locus separate from the loci encoding H-2K or H-2D alloantigens, but that the Qa-2, H-2K, and H-2D alloantigens are sufficiently related at the primary structural level to indicate that they evolved from a common primordial gene.
Amino Acid Sequence↗
Biochemical analysis of an MHC-linked hematopoietic cell surface antigen, Qa-2.
The region of the murine 17th chromosome telomeric to H-2D encodes a group of serologically defined cell surface antigens termed Qa-1-5. These antigens are of interest because their expression is restricted to hematopoietic cells. In addition, the molecular weight and subunit structure (ie, association with beta-2 microglobulin) of Qa-2 molecules are similar to H-2 and TL antigens. In the present studies, we have prepared isotopically labeled Qa-2 and H-2 molecules from mitogen-stimulated C57BL/6 spleen cells. Comparative peptide mapping of tryptic peptides from Qa-2 and H-2 molecules (Kb, DbKk, Dd) reveal that Qa-2 has a unique primary structure. However, considerable homology is indicated since 30--40% of the Qa-2 peptides cochromatograph with peptides derived from H-2Kb, H-2Db, H-2Kk, and H-2Dd. Studies by other investigators have demonstrated that similar levels of structural homology are observed when H-2K, H-2D, and H-2L tryptic peptides are analyzed. We conclude from these studies that the Qa-2 alloantigen is structurally related to a class of cell surface molecules (ie, H-2) that play critical roles in immune recognition processes. These data further suggest that the genes encoding Qa-2 and H-2 molecules have arisen from a common primordial gene.
Animals↗
Further biochemical data on Qa-2.
The Qa-2 differentiation alloantigen is coded by a gene situated between the D and Tla loci of the murine major histocompatibility complex (H-2). Qa-2-bearing protein was isolated by immunoprecipitation and found to be composed of subunits of 40 000 and 12 000 daltons by SDS polyacrylamide gel electrophoresis (PAGE). The 12 000 dalton material was identified as beta 2-microglobulin (beta 2M) by its molecular weight (SDS PAGE), charge (isoelectric focusing), antigenicity (reactivity with xenogenic anti-beta 2M), and genetics. The 40 000 dalton mol. wt. of Qa-2 heavy chains is 5 000 daltons less than that of D and K molecules (45 000 daltons). The quantity of Qa-2 isolated by immunoprecipitation was found to vary in strain-specific fashion and as much as a 15-fold difference was observed.
Animals↗
Radiographic changes in the hands following childhood frostbite injury.
Three young adult patients who had sustained severe frostbite of the hands as children were recently evaluated for progressive deformity and joint pain in the fingers. Characteristic radiographic abnormalities including dwarfing of the middle and distal phalanges, irregular and malapposed articular surfaces, malalignments at the proximal and distal interphalangeal joints, and evidence of degenerative arthritis in the interphalangeal joints were observed. The metacarpal phalangeal joints and wrists were spared in all patients, and fingers which had been protected from the initial cold injury were similarly not affected. Articular abnormalities and phalangeal deformity are most likely due to direct chondrocyte injury following freezing, but microvascular damage may also contribute to abnormal cartilage growth. A history of severe frostbite as a child should alert the clinician to the possibility of finger deformity and arthritis developing years after the initial injury.
Adolescent↗
New complexities at the Qa-1 locus.
Mouse strain and tissue distribution analyses indicate that the new antiserum A anti-A-Tlab recognizes the cell-surface product governed by the previously serologically undetectable Qa-1b allele. This cell-surface product has therefore been called Qa-1.2. Three levels of anti-Qa-1.2 cytotoxicity in the presence of complement have been observed: high, intermediate, and zero lysis. In general, high levels of lysis correlate with the presence of the Qa-1b allele, while zero levels of lysis correlate with the presence of the Qa-1a allele. The A.CA strain reacts with both anti-Qa-1.1 and anti-Qa-1.2 and may possess a third allele, Qa-Id. Several strains including B6-H-2k react in an intermediate fashion. Recombinant strain analyses indicate that this intermediate reaction may be due to modifying genes within the H-2D region.
Alleles↗
Psychosis during adolescence. A review.
All indicators of emotional illness rise sharply during adolescence including the utilization of outpatient psychiatric clinics and hospitalizations for psychiatric illness and suicide. Psychoses secondary to drug ingestion, manic-depressive illness, and schizophrenia are not uncommon. This paper reviews the various forms of psychoses during adolescence. Special emphasis is on the diagnosis and treatment of adolescent schizophrenia, the most common psychosis in this developmental period.
Adolescent↗
The Qa-1 alloantigens. I. Identification and molecular weight characterization of glycoproteins controlled by the Qa-1a and Qa-1b alleles.
Splenocytes from the Qa-Tla congenic strain pairs, A and A-Tlab or B6 and B6-Tlaa, were biosynthetically labeled with 3H-amino acids or cell surface labeled with 125I. Membrane proteins were solubilized with detergent and chromatographed on lentil lectin-Sepharose, and the resulting adherent pools were immunoprecipitated with antisera specific for determinants controlled by the Qa-1a and Qa-1b alleles, Qa-1.1 and Qa-1.2, respectively. Polyacrylamide gel electrophoresis analysis of immunoprecipitates from biosynthetically labeled preparations indicated that both the Qa-1.1 and Qa-1.2 antigens were glycoproteins with a m.w. of approximately 46,000. Qa-1.2 isolated from radioiodinated spleen cells similarly had a m.w. of 46,000. Analysis of anti-Qa-1.1 precipitates from 125I-labeled Qa-1a lysates demonstrated in addition to the 46,000 m.w. component, an electrophoretically heterogeneous protein or series of proteins in the m.w. range of 55,000 to 75,000. The specificity of these reactivities was shown by both antiserum and genetic control immunoprecipitations. These findings indicate that the Qa-1.1 and Qa-1.2 antigens are cell surface glycoproteins that are distinct from the TL antigens, and suggest a further complexity at the Qa-1--Tla locus.
Alleles↗
Induction of surface Qa2 on lymphoid cells.
Three tumor cell lines isolated from individual murine sarcoma virus-infected BALB/cBy (Qa2-) mice were established. BOMS, ORA I, and Thorbly I were analyzed for the expression of Qa2 and Ly surface differentiation antigens. By Cytofluorograf analysis and absorption techniques, all 3 cell lines were found to be Qa2+, Ly1-, Ly2-. This cell surface phenotype suggests that immature lymphoid cells are uniquely susceptible to transformation by virus. Anomalous appearance of Qa2 on transformed lymphoid cells may be analogous to TL antigen induction.
Animals↗
A new allele and antigen at the Tla locus.
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Alleles↗