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Immunoglobulin:
Isotypes, Allotypes and Idiotypes
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Human IgM
antiserumReacts with
IgM, IgG, IgA, IgD, IgE
React with IgG, IgA, IgD and IgE
Absorbed antiserum Reacts only with IgM
Recognizes determinants
specific for heavy chains
(isotypes)
Immunoglobulin Isotypes
??
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Immunoglobulin Allotypes
Definition - Antigenic determinants specified
by allelic forms of the Ig genes
Location
Occurrence
Source of anti-allotypic Abs
IgG1 (kappa)
Person 2
IgG1 (kappa)
Person 1
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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 designatednumber or letter in
brackets
Chain Domain AllotypeAminoAcid
Position
CH1 G1m(f) = (3) Arg 214
CH1 G1m(z) = (17) Lys 214
IgG1
CH3 G1m(a) = (1) Arg, Asp,Glu, Leu
355-358
CL Km(1) Val, Leu 153, 191lightchain CL Km(3) Ala, Val 153, 191
In humans allotypes are encounteredwithin: 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
Chain Domain AllotypeAminoAcid
Position
CH1 G1m(f) = (3) Arg 214
CH1 G1m(z) = (17) Lys 214
IgG1
CH3 G1m(a) = (1) Arg, Asp,Glu, Leu
355-358
CL Km(1) Val, Leu 153, 191lightchain CL Km(3) Ala, Val 153, 191
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Chain Domain AllotypeAminoAcid
Position
CH1 G1m(f) = (3) Arg 214
CH1 G1m(z) = (17) Lys 214
IgG1
CH3 G1m(a) = (1) Arg, Asp,Glu, Leu
355-358
CL Km(1) Val, Leu 153, 191light
chain CL Km(3) Ala, Val 153, 191
Genetics
(pseudoalleles)
Co-dominant
G1m(17) G1m(1)
214 355-358
Human Immunoglobulin Allotypes
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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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DNP-BSAStrain A
MouseAnti-DNP Ab
Purified
anti-DNP Ab
Strain A
Mouse
Ab against
combining site of
anti-DNP Ab
Immunoglobulin Idiotypes
Antigenic
determinants
created by the
HVR = Idiotypes
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Immunoglobulin Idiotypes
Definition
Location
IgG1 (kappa)
Person 1
anti-B
IgG1 (kappa)
Person 1
anti-A
Idiotypes are localized
on the Fab fragment
specifically at or near
the HVR of heavy andlight chains
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Immunoglobulin Idiotypes
Definition
Location
Importance
V region marker
Regulation of immune responses
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Ag Id anti-Id
+
-
anti-anti-Id
+
-
Regulation by Id/anti-Id
Each therapeutic antibody is structurally unique and has thepotential 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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Ag Id anti-Id
+
-
Anti-Idiotype Vaccines
Ag Id anti-Id
+
In some cases anti-idiotypic antibodies stimulateB 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 ofGlycoconjugates in Melanoma Patients1
Mauro Alfonso2,*, Alain Daz*, Ana Mara Hernndez*, Alexis Prez*,
Edmundo Rodrguez, Roberto Bitton, Rolando Prez*and Ana Mara
Vzquez
*
*
Center of Molecular Immunology and National Institute ofOncology and Radiobiology, Havana, Cuba; and ELEA Laboratories,
Buenos Aires, Argentina
Vaccine was safe and produced the desired antibodies in 16 of 17 patients
http://www.jimmunol.org/cgi/content/full/168/5/2523http://www.jimmunol.org/cgi/content/full/168/5/2523http://www.jimmunol.org/cgi/content/full/168/5/2523http://www.jimmunol.org/cgi/content/full/168/5/25238/14/2019 06iso Allo Idio09
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Immunoglobulin Idiotypes
Definition
Location
Importance
V region marker
Regulation of immune responses
Vaccines
Treatment of B cell tumors (T cell)
Recommended