Immunoglobulin:
Isotypes, Allotypes and Idiotypes
Immunoglobulin Isotypes
• Definition - Antigenic determinants that
characterize the classes and subclasses of
heavy chains and types and subtypes of
light chains
Immunoglobulin Isotypes
Human IgM
antiserum
Reacts with
IgM, IgG, IgA, IgD, IgE
??
React with IgG, IgA, IgD and IgE
Absorbed antiserum
Reacts only with IgM
Recognizes determinants
specific for µ heavy chains
(isotypes)
Immunoglobulin Isotypes
•
•
•
•
Definition
Location
Occurrence
Importance
VH
VL
– Ig levels
– B cell tumors
CH3 + CH4
– Immunodeficiencies
CH1
CH2
IgG1 (kappa)
IgM (kappa)
Isotypic variation is present in the germline of all members of a
species producing the heavy(μ,δ,γ,ε,α) and light chains (Igκ,λ) and
the V region framework
Immunoglobulin Allotypes
• Definition - Antigenic determinants specified
by allelic forms of the Ig genes
– Source of antiallotypic Abs
• Location
• Occurrence
IgG1 (kappa)
IgG1 (kappa)
Person 1
Person 2
Human Immunoglobulin Allotypes
• Nomenclature
– G1m(3)
– Km(1)
Definition of the
heavy chain class
followed by subclass, an “m”
for marker, and
the designated
number or letter in
brackets
Domain
IgG1
CH1
G1m(f) = (3)
Arg
214
CH1
G1m(z) = (17) Lys
214
CH3
G1m(a) = (1)
355-358
CL
Km(1)
Arg, Asp,
Glu, Leu
Val, Leu
CL
Km(3)
Ala, Val
153, 191
κ
light
chain
Allotype
Amino
Acid
Chain
Position
153, 191
•In humans allotypes are encountered
within: IgG; IgA and κ light chains
•All heavy chain genes are encoded
within the same locus, they are
inherited as a complex or haplotype
Human Immunoglobulin Allotypes
• Genetics (alleles)
– Co-dominant
autosomal genes
Domain
IgG1
CH1
G1m(f) = (3)
Arg
214
CH1
G1m(z) = (17) Lys
214
CH3
G1m(a) = (1)
355-358
CL
Km(1)
Arg, Asp,
Glu, Leu
Val, Leu
CL
Km(3)
Ala, Val
153, 191
Km(1)/Km(3) X Km(1)/Km(1)
Km(1)/Km(1) and Km(1)/Km(3)
– Allelic exclusion
κ
light
chain
Allotype
Amino
Acid
Chain
Position
153, 191
Human Immunoglobulin Allotypes
• Genetics
(pseudoalleles)
– Co-dominant
G1m(17)
214
Domain
IgG1
CH1
G1m(f) = (3)
Arg
214
CH1
G1m(z) = (17) Lys
214
CH3
G1m(a) = (1)
355-358
CL
Km(1)
Arg, Asp,
Glu, Leu
Val, Leu
CL
Km(3)
Ala, Val
153, 191
G1m(1)
355-358
κ
light
chain
Allotype
Amino
Acid
Chain
Position
153, 191
Immunoglobulin Allotypes
•
•
•
•
Definition
Location
Occurrence
Importance
– Monitoring bone marrow grafts
– Forensic medicine
– Paternity testing
Immunoglobulin Idiotypes
• Definition - Unique antigenic determinants
present on individual antibody molecules or
on molecules of identical specificity
Immunoglobulin Idiotypes
DNP-BSA
Strain A
Mouse
Anti-DNP Ab
Ab against
combining site of
anti-DNP Ab
Strain A
Mouse
Purified
anti-DNP Ab
Antigenic
determinants
created by the
HVR = Idiotypes
Immunoglobulin Idiotypes
• Definition
• Location
Idiotypes are localized
on the Fab fragment
specifically at or near
the HVR of heavy and
light chains
IgG1 (kappa)
IgG1 (kappa)
Person 1
Person 1
anti-A
anti-B
Immunoglobulin Idiotypes
• Definition
• Location
• Importance
– V region marker
– Regulation of immune responses
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 patient’s genetic background, the
Disease treated, dosing regimen, etc.
Immunoglobulin Idiotypes
• Definition
• Location
• Importance
– V region marker
– Regulation of immune responses
– Vaccines
Anti-Idiotype Vaccines
+
Ag
Id
+
anti-Id
Ag
Id
anti-Id
In some cases anti-idiotypic antibodies stimulate
B cells to make antibody. This approach can be
used as a vaccine
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
Immunoglobulin Idiotypes
• Definition
• Location
• Importance
–
–
–
–
V region marker
Regulation of immune responses
Vaccines
Treatment of B cell tumors (T cell)