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V R Sutton

Publications and source records attributed to V R Sutton.

45 records · Page 3Linked to original sources

Mapping of the mouse Ly-6, Xp-14, and Gdc-1 loci to chromosome 15.

The Ly-6 locus is now regarded as a gene complex consisting of at least five closely linked loci (Ly-6A-Ly-6E) whose polymorphic products are identified by monoclonal antibodies and distinguished by different tissue distributions. Ly-6 has been assigned by other investigators to chromosome (Chr) 9 (linked to Thy-1) or to Chr 2. We report that the Ly-6 gene complex, together with the Xp-14 and Gdc-1 loci, is situated on Chr 15 linked to Gpt-1. These new linkage data are derived from four sources: (1) three separate crosses that failed to demonstrate linkage of Ly-6 to either Thy-1 on Chr 9 or to any of five genes present on Chr 2; (2) the NXSM recombinant inbred strains, which suggested the linkage of Ly-6 and Xp-14 to Gpt-1 on Chr 15; (3) several Gpt-1 and Gdc-1 congenic strains that confirmed the assignment of Ly-6 and Xp-14 to Chr 15; and (4) backcrosses that further confirmed the linkage of Ly-6, Gpt-1, Gdc-1, and Xp-14, the probable gene order being Gpt-1/Ly-6-Xp-14-Gdc-1.

Alanine Transaminase↗

Genetic and biochemical characterization of antigens encoded by the Ly-24 (Pgp-1) locus.

Three allele-specific monoclonal antibodies to Pgp-1 (Ly-24) were used to biochemically characterize the cell surface structures with which they reacted and to map the gene(s) coding for these antigens. The targets of these three monoclonal antibodies (mAb) were shown to be encoded by a gene situated on chromosome 2 close to beta 2m [gene order (Pgp-1-beta 2m-a)] and no recombination between the loci detected by the three antibodies was revealed by genetic analysis. The genetic mapping of loci and tissue distribution of these antigens suggested that they might all correspond to a particular allelic form of the mouse phagocyte glycoprotein-1 (Pgp-1) antigen. Biochemical and serological analysis confirmed that this was indeed the case and revealed that all three mAbs were directed to one epitope. It is surprising that the tissue distribution defined by one mAb (Ly-24A) was different from that for the two other (Ly-24B) antibodies, despite the serological and biochemical identity of their respective targets. The possible reason for this unusual finding is discussed.

Animals↗

Variable expression of Qa-m7, Qa-m8, and Qa-m9 antigenic determinants on primitive hemopoietic precursor cells.

Using monoclonal antibodies, we have analysed the distribution of three recently described Qa antigenic determinants (Qa-m7, Qa-m8 and Qa-m9) on murine clonable hemopoietic progenitor cells and spleen colony-forming units (CFU-S). Cytotoxicity experiments showed that Qa-m7 was expressed on almost all the progenitor cells (colony-forming cells, CFC) of megakaryocytes (MEG-CFC), erythroid cells (E-CFC), B lymphocytes (BL-CFC), and mixed colonies (MIX-CFC) as well as day 13 CFU-S, and a major proportion of granulocyte-macrophage colony-forming cells (GM-CFC) and day 8 CFU-S. Experiments using four sources of granulocyte-macrophage colony-stimulating activity suggested differential expression of Qa-m7 on subpopulations of GM-CFC, those preferentially forming macrophage colonies having lowest Qa-m7 antigen density. Immune rosetting techniques demonstrated the selective expression of Qa-m8 on approximately 50% of MEG-CFC, MIX-CFC and day 13 CFU-S, a pattern similar to that of Qa-m2. In contrast, Qa-m9 was not detected on any of the primitive hemopoietic precursors assayed. The results demonstrate the complexity of the Qa antigenic system, and suggest a possible role for these antigens in hemopoietic differentiation.

Animals↗

Identification of two forms of the Ly-6.2 antigen showing differential expression.

A monoclonal antibody to the Ly-6.2 specificity, defined by strain and tissue distribution, was used to identify the cellular antigens of lymphocytes and tumor cell lines. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immune precipitates demonstrated that the Ly-6.2 antigen on the surface of thymus and the T lymphoma EL-4 was a protein of 34 kd, whereas spleen cells showed two Ly-6.2 molecules of 34 kd and 56 kd. In vitro translation of EL-4 T-lymphoma poly A+ RNA followed by immunoprecipitation showed the synthesis of two Ly-6.2 precursor polypeptides. These two precursors were translated from separable mRNA molecules; the larger encoded a 54 kd polypeptide, while the second, smaller one translated a 36 kd polypeptide. Thus, the T lymphoma EL-4 contains two distinct mRNA, but only one is seen on the surface, while spleen cells contain and translate both mRNAs and both surface forms are detected. What determines the utilization of the two mRNAs and the surface expression of the two different proteins in the different tissues is not known. Whether the two mRNAs are the transcripts of one gene or arise by transcription of two separate but closely linked genes remains to be determined.

Animals↗

The distribution of the Qa-2 alloantigen on functional T lymphocytes.

The expression of Qa-2 on functional lymphocytes was investigated in vitro and in vivo by using a monoclonal anti-Qa-2 antibody. In vitro treatment of T cells with antibody and complement demonstrated that T cells mediating help or delayed-type hypersensitivity for anti-SRBC responses were Qa-2+. In addition, cytotoxic T cells and either their precursors or cells involved in their generation were Qa-2+, as were anti-HGG suppressor T cells. Panning techniques were also used to show that secondary suppressor T cells were Qa-2+ and that there may be heterogeneity in suppressor T cells defined by Qa-2 expression. In vivo treatment of mice with anti-Qa-2 resulted in decrease in immune responsiveness seen by i) prolongation of skin grafts with either H-2D or I-A differences, ii) suppression of delayed-type hypersensitivity, and iii) inhibition of T cell-mediated suppression. Finally, IgG, but not IgM, anti-body-forming cells were Qa-2+.

Animals↗

Definition of new alloantigens encoded by genes in the Ly-6 complex.

Three alloantigens encoded by Ly-6-linked genes are defined by monoclonal antibodies. The Ly-27.2 antigen is defined by antibody 5075-19.1, Ly-28.2 by 5075-3.6, -12.1, -16.10 and by 5095-16.6. The strain distribution pattern of these antibodies is the same and identical with Ly-6.2. However the tissue distribution of these antigens is unique and distinguishes these antigens from the Ly-6.2 antigen or any known antigen encoded by Ly-6-linked genes. Ly-27.2 is present on all thymocytes, T cells, and B cells but is absent from bone marrow cells, whereas Ly-28.2 is absent from most thymocytes and is present on a subpopulation of T cells and B cells but is found on 60-70% of bone marrow cells. No recombination between the Ly-6/Ly-27/Ly-28 loci was found in linkage studies using 41 recombinant inbred strains and 57 backcross mice and indicates very close linkage of these genes. In addition, close linkage to 24 minor histocompatibility genes was excluded using the Bailey HW bilineal congenic mice. The data presented indicate that either the Ly-6 complex is composed of a family of tightly linked genes or the antigens are the products of a single gene that undergoes extensive modification during differentiation.

Animals↗

Description of a new Qa antigenic specificity, "Qa-m9," whose expression is under complex genetic control.

The "Qa-m9" specificity has been defined by a monoclonal antibody, and evidence for three-gene control of its expression has been demonstrated. The Qa allocation was made on the basis of H-2 linkage (H-2 congenic strains, Rl lines), differential reaction with B6.K1 and B6.K2, and biochemical analysis (two chains: 39,000 Mr and 12,000 Mr). "Qa-m9" is expressed on T and B cells in spleen and lymph node; it is present on a small population of bone marrow cells but is absent from thymocytes. The three genes involved in the expression of the antigen are: a) an H-2 linked Qa gene (possibly encoded by a gene different from Qa-2-6); b) an H-3 linked gene--probably beta 2m; and c) an H-2D linked gene that controls the amount of antigen present. It is likely that the determinant is of the "combinatorial" or conformational type, whereby the C57BL/6-type Qa heavy chain and the appropriate beta 2m light chain must both be in association. Thus, the study provides evidence for a multi-gene control of antigen expression and demonstrates the potential for generating new antigens with diversity at a post-translational level.

Animals↗