Criteria that define Ab2

Several criteria have been proposed to distinguish Ab2a from Ab2f3. Immunochemical criteria are based on the molecular mimicry concept, which are predicted that all Ab2(3 resemble the antigen and therefore Abl-Ab2(3 interactions are antigen inhibitable. If this feature can distinguish Ab2u from Ab2(3, it is not sufficient on its own to distinguish Ab2f3 from Ab2y. This latter category is also antigen inhibitable but cannot elicit an antibody response to the antigen by itself.

The best criterion is a structural one. Ab23 may share some amino acid sequence with the antigen. An

Ah2(3 specific for anti-glutamic acid-alanine-tyrosine synthetic terpolymer (GAT), in which GT is the major immunodominant epitope, has a GTT surface-exposed tripeptide in the D region. The injection of this Ab2(3 into animals elicits an anti-GAT or GT response. Similarly, an Ab2(3 specific for anti-hemag-glutinin reovirus antibody shares a tetrapeptide located in the CDR2 of the variable region of the light chain with the protective epitope of viral hemagglutinin. This antibody, as well as the synthetic peptide that corresponds to its shared sequence, can elicit an anti-viral immune response and can be recognized by cytotoxic T cells specific for viral hemagglutinin. It should be noted that Ab2|3, which mimic nonprotein antigens such as polysaccharides and glycolipids, and steroidal hormones such as aldosterone, have also been described.

Perhaps the most practical criterion for defining Ab2f3 is the functional one; namely, their ability to elicit the production of Ab1 antibodies specific for the nominal antigen.

Immunization with anti-Id antibodies can, in principle, lead to the production of several types of antibody molecules: the Ag+/Id+/Abl type, which binds to nominal antigen and expresses the idiotype of the antibody used to prepare Ab2(3; the AgTd /Abl type, which binds to nominal antigen but fails to express the idiotype of the Abl used as immunogen; and Ag~Id+, which are Ab3 antibodies able to bind to the idiotype of Ab2.

In principle, the outcome of the immunization with Ab2a or Ab2y antibody will be the activation of clones producing Ag+Id+ and Ag"Id+ antibodies, since these antibodies can interact only with Abl clones bearing the corresponding idiotypes or with Ab3 clones producing only anti-anti-id antibodies. In contrast, the outcome of the immunization with Ab2p, which by virtue of its idiotypes could mimic the antigen will activate Ag+/Id+ as well as Ag^Id" clones, both of which are able to recognize the nominal antigen or its idiotypic surrogate. Obviously, Ab2 can also activate true Ab3 clones.

Therefore, the functional criterion which define an Ab23 is the ability to initiate the production of antibodies specific for nominal antigens able to express a variety of idiotypes in the absence of the immunization with antigen itself.

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