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Biomedical subjects

B BENACERRAF

Publications and source records attributed to B BENACERRAF.

At least 19 recordsLinked to original sources

GENETIC CONTROL IN GUINEA PIGS OF IMMUNE RESPONSE TO CONJUGATES OF HAPTENS AND POLY-L-LYSINE.

Random-bred Hartley strain guinea pigs which do not respond immunologically to conjugates of hapten and poly-L-lysine mere mated with heterozygous guinea pigs which do. These responders were considered heterozygous for this trait since their mating resulted in at least one nonresponder offspring. Of 31 offspring from 10 breeding pairs (nonresponder x heterozygous responder) 14 were responders. There was no evidence that this trait is sex-linked. This finding confirms the view that, in guinea pigs, development of an immune response to the aforementioned conjugates is a genetically transmitted autosomal, unigenic Mendelian dominant trait.

Animals↗

STUDIES ON ANTIGENICITY. THE RELATIONSHIP BETWEEN IN VIVO AND IN VITRO ENZYMATIC DEGRADABILITY OF HAPTEN-POLYLYSINE CONJUGATES AND THEIR ANTIGENICITIES IN GUINEA PIGS.

The enzymatic degradation of fluorescein conjugates of poly-L-lysine, poly-D-lysine, and exhaustively succinylated poly-L-lysine by aqueous extracts of spleens from "responder" (guinea pigs which can develop immune responses to hapten-poly-L-lysine conjugates) and "non-responder" guinea pigs was investigated. The in vivo degradation of H(3)-tagged dinitrophenyl conjugates of these synthetic polyamino acids was also studied by measuring urinary excretion of radioactive low molecular weight degradation products of these conjugates after their intraperitoneal injection. It was found that both responder and non-responder guinea pigs can degrade succinylated and unsuccinylated poly-L-lysine conjugates into small molecular fragments, but they cannot degrade hapten-poly-D-lysine conjugates. These studies demonstrate that in addition to the known requirements for antigenicity of macromolecules, i.e. the presence of antigenic determinants, and their capacity to be degraded by immunological tissues, the resulting degradation products must undergo certain additional, as yet unidentified, specific metabolic steps in order to induce an immune response.

Animals↗

ELECTROPHORETIC SEPARATION AND PROPERTIES OF MOUSE ANTIHAPTEN ANTIBODIES INVOLVED IN PASSIVE CUTANEOUS ANAPHYLAXIS AND PASSIVE HEMOLYSIS.

Some properties of mouse antibodies produced by hyperimmunization with conjugated haptens, emulsified in complete adjuvant, have been investigated. Under these conditions two antigenically different types of precipitating antibody, with small differences in their electrophoretic mobilities, both migrating in the gamma-region, are produced. Both antibody types were shown to be different from the beta(2A)-globulins) as revealed by the absence of reaction with specific rabbit antisera against mouse beta(2A)-myeloma globulins. gamma(2) or the slower migrating antibodies, similarly to what has been described for the guinea pig, were able to provoke lysis of antigen-coated tanned sheep erythrocytes, in the presence of complement. This activity could not be detected in the faster migrating antibody type. The slower migrating fractions of the gamma(2)-antibodies were able to transfer passive cutaneous anaphylaxis (PCA) in the guinea pig, but not in their own species. gamma(1)-Antibodies were found to be capable of sensitizing the mouse for cutaneous anaphylaxis. The sensitivity of these antibodies to reduction and alkylation was different, the lytic activity being practically abolished, the PCA titers in mice much reduced, and the PCA activity in guinea pigs only partially inactivated.

Animals↗

DIFFERENCES IN THE ELECTROPHORETIC MOBILITIES OF GUINEA PIG 7S ANTIBODIES OF DIFFERENT SPECIFICITIES.

The electrophoretic mobilities of guinea pig gamma(1) and gamma(2) antibodies bearing different specificities were compared in agar gel at pH 8.2. Specifically purified antibodies bearing the same immunological specificity showed the same electrophoretic mobility, but significant differences in mobility were observed when antibodies with certain selected different specificities were compared. The specificity of the carrier protein appeared not to affect the mobilities of antihapten antibodies. Differences in mobility have also been shown between gamma(1) antihapten antibodies produced by individual guinea pigs immunized concomitantly with 2,4-dinitrophenyl bovine gamma globulin and arsanilic acid azo guinea pig albumin. The differences in the net electrophoretic charge between antibodies with different specificities roughly paralleled that of their S fragments produced by papain digestion.

Animals↗

STUDIES ON ARTIFICIAL ANTIGENS. II. THE ANTIGENICITY IN GUINEA PIGS OF ARSANILIC ACID CONJUGATES OF COPOLYMERS OF D- OR L-ALPHA-AMINO ACIDS.

An effort was made to immunize guinea pigs with arsanilic acid conjugates of copolymers of D- and L-alpha-amino acids; ASD-GAT and ASL-GAT. An immune response was observed only in the case of ASL-GAT. Antibodies specific for the arsanilic acid hapten were produced which could also react with ASD-GAT or ASGPA. These findings indicate that the proper metabolism of the antigen may be essential to the induction of the immune response.

Alanine↗

STUDIES ON ARTIFICIAL ANTIGENS. III. THE GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAPTEN-POLY-L-LYSINE CONJUGATES IN GUINEA PIGS.

The genetic transmission of the capacity to develop an immune response to hapten-polylysine conjugates was studied in guinea pigs. 82 per cent of the 22 offspring of 8 pairs of responder (guinea pigs which are capable of an immune response) parents were also responders, whereas, none of the 26 offspring of 9 pairs of non-responder parents were responders. None of 11 strain 13 guinea pigs and 100 per cent of 40 strain 2 guinea pigs were responders. These findings are consistent with the view that the capacity to respond immunologically to hapten-polylysine conjugates is genetically transmitted as a unigenic Mendelian dominant.

Animals↗

PROPERTIES OF GUINEA PIG 7S ANTIBODIES. V. INHIBITION BY GUINEA PIG GAMMA-2 ANTIBODIES OF PASSIVE IMMUNE LYSIS PROVOKED BY GAMMA-2 ANTIBODIES.

Passive immune lysis of antigen-coated erythrocytes provoked in vitro by guinea pig gamma(2) antihapten antibodies in the presence of complement, is inhibited by guinea pig gamma(1) antibodies directed against the same specificity. This inhibition of the lytic effect of complement-fixing gamma(2) antibodies is presumably due to the competition for antigen by non-lytic gamma(1) antibodies.

Animals↗

STRUCTURE AND SPECIFICITY OF GUINEA PIG 7S ANTIBODIES.

Additional evidence has been obtained to show that different guinea pig anti-hapten antibodies differ in the structure of their L polypeptide chains. Antibodies from animals immunized with the same hapten conjugated to different carrier proteins gave similar starch gel electrophoretic patterns after dissociation of their chains. In a study of fine differences of specificity, cross-reacting antibodies were found to have some L chains with the same electrophoretic mobility. The multiplicity of L chain bands found in the characteristic starch gel electrophoretic patterns of dissociated anti-DNP antibodies was shown to be a reflection of the heterogeneity of antibodies of slightly different specificities. Reduction and alkylation of the active fragment produced by digestion of antibodies with papain yielded starch gel electrophoretic bands corresponding in mobility to L chains. The results are consistent with the notion that L chains are involved in the acquisition of immunologic specificity.

Animals↗

Properties of guinea pig 7S antibodies. I. Electrophoretic separation of two types of guinea pig 7S antibodies.

Guinea pigs hyperimmunized with single protein antigens or hapten conjugates emulsified in complete adjuvants produced two types of precipitating antibodies with different electrophoretic mobilities. "Slow" migrating antibody generally appeared earlier and "fast" migrating antibody later in the course of immunization. Animals initially immunized by the intraperitoneal route with hapten conjugates without adjuvants produced primarily fast migrating antibody. Purified guinea pig antibodies were also separable into slow and fast migrating components by electrophoresis in supporting media. Using suitable antisera prepared in rabbits hyperimmunized with guinea pig serum, it was demonstrated that slow and fast antibodies have both common and distinct antigenic determinants. Analytical ultracentrifugation disclosed that both antibodies have sedimentation coefficients of approximately 7S. These antibodies have been designated guinea pig 7Sgamma(1) and 7Sgamma(2).

Animals↗

Properties of guinea pig 7S antibodies. II. Identification of antibodies involved in passive cutaneous and systemic anaphylaxis.

Guinea pig 7Sgamma(1) antibodies were demonstrated to mediate passive systemic or cutaneous anaphylaxis; guinea pig 7Sgamma(2) antibodies were unable to mediate these reactions. Gamma-2 antibodies specifically inhibited passive cutaneous anaphylactic reactions provoked by gamma-1 antibodies by competing for antigen. However, gamma-2 antibodies were unable to inhibit passive cutaneous sensitization of guinea pigs by a heterologous antibody system. Guinea pig 7Sgamma(2) antibodies appear to lack receptors for fixation to guinea pig tissues and do not compete with sensitizing antibody for receptor sites.

Anaphylaxis↗

Properties of guinea pig 7S antibodies. III. Identification of antibodies involved in complement fixation and hemolysis.

Guinea pig 7Sgamma(2) antibodies were demonstrated to fix complement in the presence of antigen and to sensitize antigen-coated, tanned erythrocytes for lysis in the presence of complement; guinea pig 7Sgamma(1) antibodies did not participate in these reactions. Gamma-2 antibodies were more efficient in provoking hemorrhagic necrosis in reverse passive Arthus reactions than equal amounts of non-complement-fixing gamma-1 antibodies. Unlike anaphylaxis in the guinea pig, both guinea pig 7Sgamma(1) and 7Sgamma(2) antibodies provoked passive cutaneous anaphylactic reactions in the rat. Efficient hemolytic activity attributable to 7S guinea pig anti-sheep erythrocyte antibodies migrated faster than the peak of complement-fixing activity, but slower than the peak of PCA activity in starch block electrophoresis. It is uncertain whether this activity is a function of a third type of antibody produced in response to the particulate property of the antigen or whether it is due to the antigenic heterogeneity of the erythrocyte cell membrane.

Anaphylaxis↗