Cellular Aspects of the Inverse Relationship between the Net Charge of Immunogens and of Antibodies Elicited

Sela, Michael; Mozes, Edna; Shearer, Gene M.; Karniely, Yuval

doi:10.1073/pnas.67.3.1288

Cited by 26 publications

(24 citation statements)

References 10 publications

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“…This inverse net charge phenomenon has a cellular basis for both positively and negatively charged immunogens as demonstrated by cell separation techniques over columns of opposite charge (7,8) . Mouse spleen cells eluted from glass bead columns or poly-L-lysine-coated glass bead columns comprised 35 or 20% of the whole cell suspension, respectively .…”

Section: Discussionmentioning

confidence: 99%

“…The cellular basis ofthe net charge phenomenon has been established for both positively and negatively charged immunogens, by cell separation techniques over columns of opposite charge (7,8). To establish whether this phenomenon can be extended to include cell-mediated immunity, the response to basic encephalitogenic protein (BE) which induces experimental allergic encephalomyelitis (EAE) was now investigated .…”

Section: Discussionmentioning

confidence: 99%

“…were prepared according to the method described by Sela et al . (7). Poly-L-lysine-coated glass beads were prepared as described by Karniely et al .…”

Section: Methodsmentioning

confidence: 99%

“…These hapten-specific antibodies differed in net electrical charge, but were indistinguishable with respect to their specificity and affinity (6). It has been previously established that the inverse net charge phenomenon has a cellular basis (7,8) . Thus, the immune response potential ofmouse spleen to the 2,4-dinitrophenyl hapten attached to a negatively charged synthetic polypeptide carrier was reduced by cell fractionation over negatively charged glass bead columns, whereas the response to the same hapten on a positively charged carrier was unaffected (7).…”

mentioning

confidence: 99%

“…It has been previously established that the inverse net charge phenomenon has a cellular basis (7,8) . Thus, the immune response potential ofmouse spleen to the 2,4-dinitrophenyl hapten attached to a negatively charged synthetic polypeptide carrier was reduced by cell fractionation over negatively charged glass bead columns, whereas the response to the same hapten on a positively charged carrier was unaffected (7). Furthermore, spleen cells fractionated over positively charged poly-L-lysine-coated glass bead columns showed reduced response potential to the dinitrophenyl hapten on the positively charged carrier only.…”

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confidence: 99%

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Inverse relationship between net electric charge on the antigen and that on the sensitized cell in cellular immune response: demonstration with basic encephalitogen of the brain.

Teitelbaum¹,

Webb²,

Rauch³

et al. 1975

The Journal of Experimental Medicine

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An inverse relationship has been demonstrated between the net electrical charge of immunogens and the charge of the antibodies elicited by them (1-3). IgG antibodies to natural and synthetic negatively charged immunogens were found in the first, more basic, fraction of immunoglobulin eluted from diethylaminoethyl Sephadex A-50 . In contrast, the antibodies elicited by basic immunogens appeared in the second, more acidic, eluted fraction (1-5). This observation has been extended to include antihapten antibody responses generated by groups such as 2,4-dinitrophenyl and a tetrapeptide Of D-alanine, attached to positively and negatively charged carriers (1, 2, 6) . These hapten-specific antibodies differed in net electrical charge, but were indistinguishable with respect to their specificity and affinity (6). It has been previously established that the inverse net charge phenomenon has a cellular basis (7,8) . Thus, the immune response potential ofmouse spleen to the 2,4-dinitrophenyl hapten attached to a negatively charged synthetic polypeptide carrier was reduced by cell fractionation over negatively charged glass bead columns, whereas the response to the same hapten on a positively charged carrier was unaffected (7). Furthermore, spleen cells fractionated over positively charged poly-L-lysine-coated glass bead columns showed reduced response potential to the dinitrophenyl hapten on the positively charged carrier only.It was established that the cell population relevant for the charge properties of immunogens was of thymus and not of marrow origin, by experiments in which thymocytes and bone marrow cells were selectively passed over positively or negatively charged columns and mixed with unfractionated cells of the complementary type (8). Thus, thymocytes fractionated over negatively charged columns and mixed with unfractionated marrow cells exhibited reduced antibody response to the hapten on the negative carrier but normal responses to hapten

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…were prepared according to the method described by Sela et al . (7). Poly-L-lysine-coated glass beads were prepared as described by Karniely et al .…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Inverse relationship between net electric charge on the antigen and that on the sensitized cell in cellular immune response: demonstration with basic encephalitogen of the brain.

Teitelbaum¹,

Webb²,

Rauch³

et al. 1975

The Journal of Experimental Medicine

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Antibodies against polyalanyl determinants attached to negatively or positively charged carriers

1971

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This specificity is also shown b y absorption data, results that, in addition, confirmed the basic concept of anti-RS antiserum formation. That lymphoid cells from animals that were not expected to possess a particular RS, such as those from, for instance, (A x C57BL/6) F1 hybrids or from A mice in the case of RS(A), failed to neutralize serum anti-RS(A), strongly favors the view that animals lacking a particular RS may be provoked to produce an antiserum to that RS. As far as neutralization of anti-RS activity by absorption with lymphoid cells is concerned, failure t o neutralize extended even t o lymphoid cells from specifically tolerant animals. This result merely reflects classical ideas on transplantation tolerance implying central failure of t h e immune system t o the tolerated antigens [ 11. Of course, neutralization of a particular murine anti-RS serum should be possible b y absorption with any mouse lymphoid cells carrying corresponding RS. Results t o b e published will demonstrate the validity of this fact. A complication of these experiments stems from the fact that parental strain lymphoid cells used t o immunize F 1 hybrids are, for genetic reasons, accepted by the hosts and are thus able to form classical alloantibodies against the transplantation antigens of the other parental strain present in the hybrids. Such antibodies could have an "enhancementlike" effect o n the recognition process by masking of the antigenic target. Appropriate experiments have shown that this is indeed the case. The effect can be easily distinguished from the anti-RS activity discussed here: it addresses itself t o the target cell of immunological one-way reactions and obeys opposite laws of absorption. The Weizmann Institute of Science, Rehovot Antibodies against polyalanyl determinants attached to negatively or positively charged carriers Polyalanyl determinants, when attached to acidic or basic carriers, provoke a specific anti-polyalanyl antibody population, the majority of which possesses an electrical charge which is inversely related t o that of the carrier. The .alanine chains in the immunogens form complete determinants and the contribution of the carrier t o the specificity of the antibodies is minimal. The antipolyalanyl antibodies, when fractionated into a more acidic and a more basic fraction, possess similar properties of their combining sites, as judged from hapten inhibition and equilibrium dialysis studies. Thus, the specificity of the antibodies and the combining site features are determined by the hapten determinants, whereas the net charge of the antibodies is determined by the net charge of the immunogen. The difference in the net electrical charge of the antibodies may reflect differences in areas of the molecule other than the combining site. A comparison of anti-polyalanyl antibodies obtained with different carriers has shown that the specificity and size of the combining sites are similar regardless of the nature of the carrier molecule, whereas different affinities of the antibodies are obtained...

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The influence of the net charge of antigen on the distribution of bovine IgG class antibodies

et al. 1973

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It has previously been shown that bovine immunoglobulins of the more positively charged IgGz class are confined exclusively to the serum and are incapable Max-Planck-lnstitut fur I mmunbiologie, Freiburg/Brsg. of being transferred t o the colostrum by t h e dry mammary gland. Since recent studies have demonstrated that antigens with a negative net charge preferentially provoke the synthesis of more positively charged antibodies, it could be expected that antibodies against such antigens would not be transferred t o the colostrum. In the present study, however, acidic antigens (p-azobenzenearsonate edestin and its maleylated derivative) failed t o stimulate predominantly the synthesis of precipitating, binding and phage neutralizing antibodies of the positively charged IgC, class. As expected, immunization of cattle with iysozyme, (a basic antigen), resulted in the production of antibodies almost exclusively confined to the more negatively charged IgG, fraction. In analyzing the precipitin reaction of IgG, class antibodies, it could be shown that maximum precipitation was achieved at pH 5.0 and decreased significantly at higher pH values.

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Cellular Aspects of the Inverse Relationship between the Net Charge of Immunogens and of Antibodies Elicited

Cited by 26 publications

References 10 publications

Inverse relationship between net electric charge on the antigen and that on the sensitized cell in cellular immune response: demonstration with basic encephalitogen of the brain.

Inverse relationship between net electric charge on the antigen and that on the sensitized cell in cellular immune response: demonstration with basic encephalitogen of the brain.

Antibodies against polyalanyl determinants attached to negatively or positively charged carriers

The influence of the net charge of antigen on the distribution of bovine IgG class antibodies

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