Biomedical subjects

P E Korty

Publications and source records attributed to P E Korty.

6 recordsLinked to original sources

PubMed1994

Use of the receptor globulin technology to search for ligands for glycosylphosphatidylinositol-linked cell surface antigens.

The ability of monoclonal antibodies to several proteins coupled to the membrane by a glycosylphosphatidylinositol anchor to induce T cell activation has suggested that these proteins interact with cellular ligands or counter-receptors. The murine Ly-6 antigens and the closely-related human CD59 antigen play important roles in T cell activation, B cell activation and cell-cell interactions. Receptor globulins containing the external domains of Ly-6A.2 or CD59 coupled to hinge-CH2-CH3 regions of human IgG1 were generated. When these fusion proteins were used to stain lymphoid tissues, they selectively reacted with B lymphocytes. On mouse B cells, their target antigen is membrane IgM, while their target on human B cells has not been fully defined. These results suggest that Ly-6/CD59-IgM may be a receptor-counter-receptor pair and may play a role in T-B cell interactions.

Animals↗

PubMed1991

CD59 functions as a signal-transducing molecule for human T cell activation.

The CD59 Ag is a 20-kDa protein that is widely expressed on most leukocytes and RBC, is coupled to the membrane by a phosphatidylinositol-glycan anchoring structure, plays a role in cell interaction between monocytes and T cells, and also functions as an inhibitor of cytolysis by the terminal C components C5b-9. Because this molecule is structurally related to the murine Ly-6 family of Ag, we have investigated whether anti-CD59 mAb might be capable of activating human T lymphocytes in a manner similar to that described for antibodies to the murine Ly-6 Ag. In the presence of the appropriate co-stimulators, mAb to one of the two epitopes on CD59 were capable of inducing both a rise in intracytoplasmic free Ca2+, inositol phosphate production, IL-2 production, and T cell proliferation. Anti-CD59-induced inositol phosphate turnover and IL-2 production were dependent on co-expression of the CD3/TCR complex. CD59-loss mutants of the Jurkat cell line were completely responsive to stimulation by anti-CD3 thereby demonstrating that CD59 does not play a role as a signal transducer downstream from the TCR. Taken together, these results demonstrate that the CD59 Ag can play multiple distinct roles in the regulation of the immune response.

Antibodies, Monoclonal↗

PubMed1989

Ly-6: a multigene family in search of a function.

Differentiation antigens can be simply defined as cell surface antigens that distinguish one cell type from another. The Ly-6 family of cell surface antigens might easily be regarded as a prototype for the analysis of the function of differentiation antigens on immunocompetent cells. Although a number of studies with antisera, in the late 1970s, established that the Ly-6 antigens exhibit an unusual pattern of expression on T and B lymphocytes, functional studies failed to demonstrate that the expression of Ly-6 defines a unique subpopulation of immunocompetent cells. Paradoxically, the development of anti-Ly-6 monoclonal antibodies led to a further decline in interest in this group of antigens, as the complexity of the results relegated Ly-6 to the realm of the die-hard immunogeneticist. Over the past five years, interest in Ly-6 has been rekindled and in this review Ethan Shevach and Patricia Korty summarize recent studies on the serology, biochemical and molecular structure, and the function of the products of this multigene family.

Amino Acid Sequence↗

PubMed1988

A single cDNA encodes multiple Ly-6 antigenic specificities.

To determine the relationship between the structure and function of proteins coded for by the Ly-6 gene complex, we have transfected a cDNA for a Ly-6.2 specificity into COS-7 cells. A number of monoclonal antibodies which have been shown to be capable of inducing T cell activation and which have been previously considered to recognize distinct proteins all reacted with the same transfected gene product. The approach used in these studies should be useful to further elucidate the complexities of the Ly-6 alloantigen system.

Animals↗

PubMed1986

Role of Ly-6 in lymphocyte activation. I. Characterization of a monoclonal antibody to a nonpolymorphic Ly-6 specificity.

In studies with alloantisera and monoclonal antibodies (mAb) a number of antigenic determinants have been defined that are the products of the Ly-6 locus on murine chromosome 2 and that are expressed primarily on B and T lymphoid cells. It remains controversial whether these antigenic determinants are encoded by a single gene or a multigene complex. We have characterized a new rat mAb, D7, which recognizes a cell surface antigen whose expression on nonactivated peripheral lymphocytes varies from strain to strain. The phenotype of the staining profile, i.e., high or low percentage of D7-positive cells, mapped to the Ly-6 locus as assayed by strain distribution studies, RI lines, and Ly-6 congenic strains. The binding of D7 to Ly-6.1-positive strains could be inhibited by mAb directed to the Ly-6E.1 specificity, whereas D7 could inhibit the binding of mAb specific for Ly-6A.2 to cells from Ly-6.2-positive strains. Coprecipitation studies followed by Western blot analysis confirmed that D7 reacts with both Ly-6E.1- and Ly-6A.2-bearing molecules. The most likely explanation for these findings is that Ly-6A.2 and Ly-6E.1 represent allelic specificities. Further dissection of the complexity of the Ly-6 antigen system and determination of its possible functional importance in lymphocyte activation should be greatly facilitated by the availability of xenogeneic mAb that recognize framework determinants on multiple Ly-6 products.

Alleles↗

PubMed1986

The murine interleukin 2 receptor. IV. Biochemical characterization.

The IL 2 receptor isolated from the IL 2-dependent CTL-L cell line was subjected to biochemical analysis. Pulse-chase and tunicamycin studies, as well as digestion with the endoglycosidases, Endo-F and Endo-H, of 35S-methionine-labeled IL 2 receptors suggested a single protein precursor of 32,000 (p32) daltons. The p32 precursor was rapidly processed by addition of high-mannose-containing core N-linked sugars to intracytoplasmic precursor intermediates of 38,000 (p38) and 40,000 (p40) daltons, which undergo further processing to yield a mature surface receptor with heterogeneous apparent m.w. of 52,000 to 65,000 (p58). Two-dimensional gel studies indicated that p58 exhibited broad charge heterogeneity between pH 4.6 and 6.3. Endo-F digestions of p58 shifted the isoelectric focus point to a more basic 5.5 to 7.4. This considerable charge heterogeneity is consistent with the possibility that other posttranslational modifications to the mouse IL 2 receptor occur besides addition of complex N-linked glycans. Immunoprecipitations of the IL 2 receptor from surface iodinated cells also revealed an additional band at 110,000 (p110) daltons. IEF vs SDS-PAGE two-dimensional gel studies demonstrated that p110 also had an isoelectric focus point identical to p58. Western blot studies with an anti-IL 2 receptor monoclonal antibody (7D4) demonstrated that p38, p40, p58, and p110 each expressed the epitope recognized by this antibody. Thus, it is likely that p110 is not a unique molecule that coprecipitates with the IL 2 receptor. Western blot analysis of mitogen-stimulated T and B lymphocytes also revealed bands similar to p58 and p110, although these bands had an average apparent m.w. 3000 to 6000 less than those seen for CTL-L cells.

Animals↗