An idiotype antibody refers to a different immunogenicity of a variable region of an immunoglobulin molecule produced by a different B cell clone of the same individual, and the type distinguished thereby is called an idiotype. The idiotype-type antigenic determinants are mainly determined by the difference in amino acids in the hypervariable regions.
In the middle of this century, Ig was found to inject anti-Ig antiserum into the same or heterologous animals. It was subsequently discovered that there are two types of antigenic determinants, i.e., isoforms and allotypes, on the Ig molecule. In 1955, when Slater et al studied the specificity of rabbit anti-human myeloma protein antiserum, it was found that anti-serum protein antiserum was still used as an immunogen after being fully absorbed by other unrelated myeloma proteins or normal human Ig. The myeloma proteins react, and they refer to this new antigen-specificity present on Ig as "individual" antigenic specitficities.
Discovery
In 1963, Oudin et al. immunized 50 rabbits with Salmonella typhi, and used one of the rabbit anti-S. typhimurium antibodies isolated from the serum of rabbits as an immunogen to immunize normal rabbits and isolate the serum to obtain anti-ID antibody. The study found that this anti-antibody can only react with the anti-typhoid H. typhimurium antibody as an immunogen, but it cannot precipitate with the serum of the other 49 Salmonella typhimurium-immunized rabbits, nor can it immunize rabbits with other antigens. Serum or normal rabbit serum reacts. The above results indicate that the Salmonella typhimurium antibody produced by this rabbit has a special antigenic determinant which is different from the antigenic determinant of the antibody molecule produced by the same antigen (S. typhi) in other individuals (rabbit). Also different from the antigenic determinant on the antibody molecule produced by the same individual for different antigens, Oudin refers to this antigenic determinant different from isotype and allotype as idiotype, meaning individual genotype . Later, it was found that in most cases, different individuals have cross-reactive antibodies against the same antigen, so the idiotype is no longer considered to have strict individual differences. Idiotype is now translated as a unique type. With the advancement of research in ranking chemistry, it is further understood that the idiotype exists in the Fab segment, which is a marker encoding the variable region gene of an antibody.
Classification
(1) The unique type associated with the joint and the unique type associated with the skeleton
By observing whether αId binds to the binding of antibodies to the corresponding antigen molecules, the anti-idiotypic antibody can be divided into two categories: a unique type that inhibits the binding of antigens and antibodies, called idiotypes associated with combining. Site); a unique type that does not inhibit the binding of antigens and antibodies, called framework associated idiotypes.
(2) Private idiotypic type and cross-reactive unique type
Private (or individual) unique type
The exclusive Id (IdI) refers to a unique type unique to a specific antibody molecule. It is generally considered that the CDR3 encoded by the D gene fragment in the V region is closely related to this.
2. Cross-reactive idiotype
Cross-reactive idiotype (CRI or IdX) refers to an idiotype from different individuals but with the same specificity on an Ab or TCR, or an idiotype from an antibody with the same antigen specificity in different species. . Certain amino acid sequences (such as amino acids 54, 55) in the CDR2 region encoded by the V gene fragment are often associated with IdX, and a very small number of IdX are related to the amino acid sequence encoded by the heavy chain framework region and the J gene fragment. For example, two groups of anti-glucan monoclonal antibodies J558 and M104 prepared by immunizing BALB/c mice with dextran (Dextran), all monoclonal antibody light chains are λ type, and the two groups of monoclonal antibodies have In addition to IdX, each has an IdI. Their cross-reactive idiotypes are localized to HR(CDR)2 in the variable region; while IdI is localized to HR(CDR)3. In other words, both have a common antigenic determinant at HR2, and the antigenicity at HR3 is different from each other.
(3) Conventional unique type and regulatory unique type
1. Conventional (or traditional) Id (conventional idiotypes)
This Id does not change during the body's immune response, mainly in the natural antibodies and autoantigen receptors, the former is obtained by inheritance, and the latter has developed immune tolerance when the individual occurs. Therefore, the content of this Id in the body is very low, and it is impossible to activate the proliferation of their complementary clones, and it has no important effect on immune regulation.
2. Regulatory Idiotypes
This Id is mainly present on the antibody molecule produced by exogenous antigen stimulation, which can activate the proliferation of complementary clones, can change during the body's immune response, and participate in the regulation of the antigen response.
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