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L Flaherty

Publications and source records attributed to L Flaherty.

At least 145 records · Page 8Linked to original sources
PubMed1980

Analysis of thymus-leukemia (TL) antigens with monoclonal antibodies.

Lysates of radioiodinated thymocytes have been sequentially immunoprecipitated with monoclonal antibodies specific for thymus-leukemia (TL) antigens. The TL antigenic specificities defined by the monoclonal antibodies appear not to correspond precisely to specificities previously defined with conventional alloantisera. Nonetheless, each of two monoclonal antibodies specific for a single TL determinant was found to deplete lysates of B6.Tlaa thymocytes of all molecules precipitable by an alloantiserum specific for the conventionally defined determinants TL.1,2,3,5, and 6. These results suggest that on B6.Tlaa thymocytes, all the conventional TL antigenic specificities (TL. 1,2,3,5,6) as well as the specificities defined by the monoclonal anti-TL antibodies (TL.m2,m3) are carried by a single molecular species.

Animals↗
PubMed1979

H-Y antigen. Cell surface mapping and testosterone-induced supramolecular repatterning.

Previous work with the antibody-blocking technique showed that the map of surface components for thymocytes prefixed with paraformaldehyde is the same as the map for unfixed thymocytes, with the following exception: after exposure to anti-TL or anti-Db, TL and H-2Db occupy adjacent positions on unfixed cells but not on fixed cells. This was interpreted as an indication that activation of particular components of the surface phenotype initiates ordered changes in the display of cell-surface molecules, approximation of TL and Db in this instance. These studies have now been extended to the H-Y component on the surface of male cells. On fixed male mouse thymocytes, H-Y lies adjacent to TL and relatively distant from H-2Db, H-2Kb, H-2Lb, Lyt-1.2, and Lyt-2.2. However, on unfixed male mouse thymocytes, similarly exposed to H-Y antibody, H-Y and H-2Db are adjacent. Presumably, this engagement of H-Y sites by H-Y antibody brings H-Y and H-2Db together. Evidence that this change in pattern may be physiologically relevant comes from the finding that testosterone, but not estradiol, caused the same selective approximation of H-Y and H-2Db.

Animals↗
PubMed1979

Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies.

Two new lymphocyte antigens, provisionally designated Qat-4 and Qat-5 have been identified with two different hybridoma-derived, monoclonal AKR antiC57BL/6 antibodies. These antigens are governed by genes located to the right (distal) end of the H-2 complex, within the Qa-2,3 region. Qat-4 and Qat-5 antigens which do not seem to be identical with Qa-2,3 or TL antigens are absent from Ig/ lymphocytes and thymocytes. They are only present on a fraction of peripheral T cells. Thus, Qat-4 is expressed on 70%, and Qat-5 on 30% of splenic and lymph node T cells, Qat-4 is also found on the majority of Ig- cells from athymic nude mice. These findings illustrate the complexity of the chromosome segment between the H-2D and Tla loci and they emphasize the role of major histocompatibility complex-associated genes for the differentiation of T cells into different subpopulations with possibly distinct immunologic functions.

Animals↗
PubMed1979

Surface mapping of mouse thymocytes.

The blocking method used previously for determining the relative positions of different components of the cell surface was modified by first fixing the cells with paraformaldehyde. This technique was applied to the H-2K (K), H-2D (D), TL, Lyt-1, and Lyt-2 surface components of mouse thymocytes, and the results were compared in parallel with data obtained with the original technique with unfixed cells. Previous mapping data with unfixed cells, indicating the positions of these molecules relative to one another, were confirmed with paraformaldehyde-fixed cells, with one exception. On unfixed cells, D and TL appeared sufficiently adjacent to produce mutual interference in the attachment of anti-D and anti-TL antibodies. With paraformaldehyde-fixed cells this was not so, D and TL appearing sufficiently separated from one another to obviate interference in the attachment of anti-D and anti-TL antibodies. The previously reported close association of K with Lyt-1 and of D with Lyt-2 were demonstrable equally with unfixed and paraformaldehyde-fixed thymocytes. It is suggested that activation of D sites, and alternatively of TL sites, by antibody in the present experiments brings these two molecules into apposition and that this movement may exemplify a mechanism concerned in immunological recognition and response.

Animals↗
PubMed1979

The Qa-2 antigen on lymphocyte subpopulations. Mixed lymphocyte culture and cell-mediated lympholysis.

Treatments of spleen cells from Qa-2+ strains with Qa-2 antiserum plus complement (C) have revealed that the Qa-2 antigen is present on restricted functional lymphocyte subpopulations. Anti-Qa-2 plus C reduced the mixed lymphocyte culture response and inhibited the generation of cytolytic effector cells. This treatment, however, did not affect cytolytic effector cells once they were generated.

Animals↗
PubMed1978

Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness.

H-2 dependent and virus-specific Ir genes regulate the generation of primary virus-specific K or D restricted cytotoxic T-cell responses in vivo. The following examples have been analyzed in some detail: first, Dk restricted responses to vaccinia in Sendai viruses are at least 30 times lower than the corresponding K-restricted responses irrespective of the H-2 haplotypes (k, b, d, dxs, dxq) of K and I regions; in contrast, LCMV infection generates high responses to Dk. These findings are consistent with but do not prove that this Ir gene maps to D. Second, Db restricted responses to vaccinia and Sendai viruses are high in strains possessing the Kq or KbIb, KbaIb haplotype, are very low in strains with Kk, and relatively low in mouse strains of the KdI-Ad haplotype; LCMV generates high Db restricted response in the presence of Kk. This Ir gene for the response to vaccinia and Sendai viruses maps to K since B10.BYR (KqIkdDb) is a responder and B10.A (2R) is a nonresponder (KkIkdDb). Third, virus and K or D allele specific nonresponsiveness is dominant with variable penetrance; in heterozygous mice the nonresponder Kk allele over-rides responsiveness normally found in KbDb or KqDb combinations. Fourth, when (responder X nonresponder)F1 lymphocytes are stimulated in an environment expressing vaccinia virus plus only a high responder Kb or Kq allelle and Db, response to vaccinia Db is high; in contrast when the same F1 cells are stimulated in an environment expressing the low responder allele Kk, response to vaccinia Db is low. Thus absence of Kk during immunization allows generation of high responsive Db restricted vaccinia specific cytotoxic T cells. The Dk dependent low response to vaccinia Dk can be explained by a preclusion rule or by failure of vaccinia to complex with Db; however the analysis of Kk dependent low response to vaccinia Db does not support these explanations or that self-tolerance is responsible for this Ir effect but is compatible with the interpretation that Kk vaccinia is immunodominant over Db vaccinia. These results are discussed with respect to (a) possible mechanisms of regulation by Ir genes and (b) H-2 polymorphism and HLA-disease association.

Alleles↗
PubMed1978

Autosomal phosphoglycerate kinase linked to mouse major histocompatibility complex.

The mouse autosomal locus that determines the form of phosphoglycerate kinase found only in testes is shown here to be closely linked to but not included within the major histocompatibility complex on chromosome 17. Data are presented that strongly favor the location of this locus, designated Pgk-2, distal to H-2, Qa-1, and Qa-2, and closely associated with T1a. The Pgk-2 strain distribution pattern for 103 inbred and congenic strains of mice is given. Because Pgk-2 is polymorphic among inbred strains, it should be of value in linkage studies.

Animals↗
PubMed1978

Qa-2 and Qa-3 antigens on lymphocyte subpopulations. I. Mitogen responsiveness.

The effects of anti-Qa-2 plus C and anti-Qa-3 plus C on mitogen-induced proliferation were studied. Both of these antisera in the presence of C markedly reduced both Con A- and PHA-induced proliferation while having little or no effect on LPS-induced proliferation. LPS, Con A, and PHA cultures and cultures containing media alone, examined at 72 hr, contained high proportions of Qa-2+ and Qa-3+ cells.

Animals↗
PubMed1977

Mutation in a new H-2-associated histocompatibility gene closely linked to H-2D.

Sequential precipitations of soluble BALB/c antigen with antisera detecting private and public H-2 specificities indicated three distinct classes of molecules of 45,000 mol wt. However, only two of these classes of molecules were detectable in antigen from the loss mutant, BALB/c-H-2db. The class of molecules, detectable in the wild-type strain but missing in the mutant, does not bear private specificities but does react with an antiserum detecting H-2 public specificities. Absorption in mutant mice of the antiserum to public specificities, left antibodies specific for the antigen detectable in BALB/c but not BALB/c-H-2db. Genetic mapping studies using this specific antiserum indicated that the antigenic loss of this mutant is in a gene which maps in or close to the H-2D region, separable from the H-2K, S, G, Qa-2, and Tla regions.

Animals↗
PubMed1977

Molecular similarities between the Qa-2 alloantigen and other gene products of the 17th chromosome of the mouse.

The alloantigen Qa-2, whose gene is located on the 17th chromosome between H-2D and Tla, is identified as a molecule of 43,000 daltons which is associated with beta 2-microglobulin. Qa-2 comprises approximately 0.15% of the iodinateable cell surface protein of lymph node cells. Sequential precipitations demonstrated that Qa-2 is distinct from H-2D and H-2K molecules.

Animals↗
PubMed1977

The Tla locus: a new allele and antigenic specificity.

Four of 23 H-2 alloantisera screened for anti-TL activity contained such activity. One of these alloantisera, D-35, defined a new TL specificity, TL.5, and a new Tla allele, Tlad. TL.5 has all the characteristics of a TL antigen and has a different strain distribution than previously known ones. This new complexity at the Tla locus and the previous finding of other serologically defined genes in the Tla region indicate that this genetic region cannot be ignored in analyzing antisera produced in strains made congenic for the major histocompatibility complex.

Alleles↗