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Biomedical subjects

M Sela

Publications and source records attributed to M Sela.

At least 235 records · Page 13Linked to original sources
PubMed1975

The specific cytotoxic effects of daunomycin conjugated to antitumor antibodies.

Daunomycin was covalently bound to immunoglobulins by periodate oxidation as described in the preceding paper. Conjugates were prepared with immunoglobulins directed against either of two mouse lymphoid tumors or with nonspecific immunoglobulins. These conjugates were tested for their toxic effects on various tumor target cells as measured either by their inhibition of RNA synthesis or by their reduction of the growth of the tumor cells after transplantation. We found that the drug preferentially affected the target cells that the antibody to which it was attached could recognize. These daunomycin-antibody conjugates are therefore sufficiently toxic and selective in their effects to be potentially useful in in vivo therapeutic studies.

Animals↗
PubMed1974

Antibody response of inbred mouse strains to ordered tetrapeptides of tyrosine and glutamic acid attached to multichain polyalanine or polyproline. Tyr-Tyr-Glu-Glu is a major determinant of the random poly-(Tyr, Glu)-polyDLAla--polyLys.

Five inbred mouse strains which represent high and low responders to the random synthetic polypeptide poly(LTyr,LGlu)-polyDLAla--polyLLys, designated (T, G)-A--L, to which the immune response is controlled by an H-2-linked gene, were immunized with three ordered tetrapeptides composed of tyrosine and glutamic acid attached either to multichain poly-DL-alanine or to polyproline. Only one of the three antigenic determinants, namely tyrosyl-tyrosyl-glytamyl-glutamic acid (T-T-G-G), resembled the random peptide (T, G) in the pattern of immune responses elicited against it, and in the cross-reactivity of the specific antibodies with (T, G)-A--L. The immune response pattern to the other two ordered tetrapeptides, T-G-T-G and G-T-T-G, was different from that obtained with (T, G)-A--L, and no cross-reactivity was detected between the antibodies provoked with these peptides and (T, G)-A--L. Thus, it is suggested that T-T-G-G is a major determinant in the random (T, G)-A--L.

Alanine↗
PubMed1974

Thymus independence of a collagen-like synthetic polypeptide and of collagen, and the need for thymus and bone marrow-cell cooperation in the immune response to gelatin.

Several inbred mouse strains were screened for their ability to respond to the ordered periodic collagen-like polymer (Pro-Gly-Pro)(n), to the random copolymer (Pro(66), Gly(34))(n), to the protein conjugate Pro-Gly-Pro-ovalbumin, to rat tail tendon collagen, rat tail tendon gelatin, and to Ascaris cuticle collagen. Differences were obtained in the magnitude of the antibody titers towards the above immunogens among the strains tested. The level of the response to the ordered polymer (Pro-Gly-Pro)(n) was not similar to that towards the random (Pro(66), Gly(34))(n), confirming differences in the antigenic determinants of the two immunogens. The role of the thymus in the immune response to (Pro-Gly-Pro)(n) and (Pro(66), Gly(34))(n) as well as to two collagens and gelatin, was studied in order to find out a possible correlation with the structural features of the immunogens. Heavily irradiated recipients were injected with syngeneic thymocytes, marrow cells, or a mixture of both cell populations and were immunized with the above-mentioned antigens. An efficient immune response to the ordered collagen-like (Pro-Gly-Pro)(n) was obtained in the absence of transferred thymocytes. The thymus independence of (Pro-Gly-Pro)(n) was confirmed when thymectomized irradiated mice were used as recipients. In contrast with these results, cooperation between thymus and marrow cells was necessary in order to elicit an immune response to (Pro(56), Gly(34))(n). Similarly, the immune response to the triple helical collagen was found to be independent of the thymus, whereas for an effective response to its denatured product, gelatin, thymus cells were required. These findings indicate that a unique three-dimensional structure of immunogens possessing repeating antigenic determinants plays an important role in determining the need for cell to cell interaction in order to elicit an antibody response.

Animals↗
PubMed1974

The role of the thymus in a genetically controlled defect of the immune response at the carrier level.

The genetic control of the immune response may be either specific for antigenic carrier or for determinant. We describe here results which show that a carrier-dependent strain defect in immune response is reflected in thymocytes. These results are in agreement with our hypothesis that the genetic defect in the immune response is reflected in thymocytes when the poor response is at the carrier level, whereas it is expressed in the bone marrow population when the low responsiveness is strictly at the determinant level. SWR mice are low responders to multichain polyproline. Furthermore, this mouse strain does not produce antibodies to determinants such as peptides of phenylalanine and glutamic acid (Phe,Glu) or to the loop peptide of lysozyme when attached to polyproline, although they respond well to the same antigenic determinants when conjugated to multichain poly(DL-alanine). Transfer experiments in which irradiated SWR recipients were injected with excess of DBA/1 thymocytes (which do not exhibit a defect in response to polyproline) mixed with graded numbers of SWR marrow cells, prior to immunization with poly(Tyr,Glu)-poly(Pro)--poly(Lys), have indicated that the poor response potential of SWR mice to polyproline is not reflected in their bone marrow cells. Allogeneic transfers in which mixtures of thymocytes and marrow cells from high and low responders were injected into irradiated mice, followed by immunization with poly(Tyr,Glu)-poly(Pro)--poly(Lys) or poly(Phe,Glu)-poly(Pro)--poly(Lys) have demonstrated a clear defect in the thymus derived population of SWR mice when the response potential to polyproline and to determinants attached to it was tested.

Animals↗
PubMed1974

Antibodies to yeast phenylalanine transfer ribonucleic acid are specific for the odd nucleoside ) in the anticodon loop.

Antibodies with specificity to a single species of tRNA were elicited in a goat by immunization with a glutaraldehyde conjugate of yeast phenylalanine transfer RNA with bovine gamma globulin. The specificity of the antibodies was studied by a radioimmunoassay measuring the direct binding of [(3)H]tRNA(Phe) or the inhibition of the binding. The antibodies formed are predominantly directed towards the characteristic highly modified nucleoside Y, which is located right next to the anticodon. The antibodies bind specifically to tRNA(Phe), to oligonucleotides derived by enzymatic digestion from the anticodon loop of tRNA(Phe), and to the Y nucleoside itself. tRNA species which do not contain Y in their sequences, or tRNA(Phe) from which the Y base has been excised, do not bind to the antibodies. Yeast tRNA(Phe) can be separated from other tRNA species with an immunoadsorbent of antibodies to tRNA(Phe).

Animals↗