Immunoglobulin: Isotypes, Allotypes and Idiotypes

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ImmunoglobulinIsotypes, Allotypes and Idiotypes
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Immunoglobulin Isotypes

• Definition - Antigenic determinants that
  characterize the classes and subclasses of heavy
  chains and types and subtypes of light chains

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Immunoglobulin Isotypes
Human IgM
Reacts with IgM, IgG, IgA, IgD, IgE
??
antiserum
React with IgG, IgA, IgD and IgE
Absorbed antiserum
Reacts only with IgM
Recognizes determinants specific for µ heavy
chains (isotypes)
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Immunoglobulin Isotypes

• Definition

• Location

VH
VL

• Occurrence
• Importance
• Ig levels
• B cell tumors
• Immunodeficiencies

CH1
CH2
CH3 CH4
Isotypic variation is present in the germline of
all members of a species producing the
heavy(µ,d,?,e,a) and light chains (Ig?,?) and the
V region framework
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Immunoglobulin Allotypes

• Definition - Antigenic determinants specified
• by allelic forms of the Ig genes

• Source of anti-allotypic Abs

• Location

• Occurrence

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Human Immunoglobulin Allotypes

• Nomenclature
• G1m(3)
• Km(1)
• Definition of the
• heavy chain class
• followed by sub-
• class, an m
• for marker, and
• the designated
• number or letter in
• brackets

• In humans allotypes are encountered
• within IgG IgA and ? light chains
• All heavy chain genes are encoded
• within the same locus, they are
• inherited as a complex or haplotype

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Human Immunoglobulin Allotypes

• Genetics (alleles)
• Co-dominant
• autosomal genes

Km(1)/Km(3) X Km(1)/Km(1)
Km(1)/Km(1) and Km(1)/Km(3)

• Allelic exclusion

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Human Immunoglobulin Allotypes

• Genetics (pseudoalleles)
• Co-dominant

G1m(17)
G1m(1)
214
355-358
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Immunoglobulin Allotypes

• Definition
• Location
• Occurrence
• Importance
• Monitoring bone marrow grafts
• Forensic medicine
• Paternity testing

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Immunoglobulin Idiotypes

• Definition - Unique antigenic determinants
  present on individual antibody molecules or on
  molecules of identical specificity

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Immunoglobulin Idiotypes
Strain A Mouse
Anti-DNP Ab
DNP-BSA
Ab against combining site of anti-DNP Ab
Strain A Mouse
Purified anti-DNP Ab
Antigenic determinants created by the HVR
Idiotypes
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Immunoglobulin Idiotypes

• Definition
• Location

Idiotypes are localized on the Fab
fragment specifically at or near the HVR of heavy
and light chains
IgG1 (kappa) Person 1 anti-B
IgG1 (kappa) Person 1 anti-A
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Immunoglobulin Idiotypes

• Definition
• Location
• Importance
• V region marker
• Regulation of immune responses

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Regulation by Id/anti-Id


Ag
Id
anti-Id
anti-anti-Id
-
-
Each therapeutic antibody is structurally unique
and has the potential to provoke immune response
in the recipients. These antibodies are called
anti-idiotypic antibodies and their Generation
depends on the patients genetic background,
the Disease treated, dosing regimen, etc.
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Immunoglobulin Idiotypes

• Definition
• Location
• Importance
• V region marker
• Regulation of immune responses
• Vaccines

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Anti-Idiotype Vaccines
In some cases anti-idiotypic antibodies
stimulate B cells to make antibody. This approach
can be used as a vaccine
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Example of an Anti-Idiotype Vaccine

• The Journal of Immunology, 2002, 168
  2523-2529.
• An Anti-Idiotype Vaccine Elicits a Specific
  Response to N-Glycolyl Sialic Acid Residues of
  Glycoconjugates in Melanoma Patients1
• Mauro Alfonso2,, Alain Díaz, Ana María
  Hernández, Alexis Pérez, Edmundo Rodríguez,
  Roberto Bitton, Rolando Pérez and Ana María
  Vázquez Center of Molecular Immunology and
  National Institute of Oncology and Radiobiology,
  Havana, Cuba and ELEA Laboratories, Buenos
  Aires, Argentina
• Vaccine was safe and produced the desired
  antibodies in 16 of 17 patients

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Immunoglobulin Idiotypes

• Definition
• Location
• Importance
• V region marker
• Regulation of immune responses
• Vaccines
• Treatment of B cell tumors (T cell)