View
218
Download
0
Category
Preview:
Citation preview
8/11/2019 06iso-allo-idio09 (1)
1/18
Immunoglobulin:
Isotypes, Allotypes and Idiotypes
8/11/2019 06iso-allo-idio09 (1)
2/18
Immunoglobulin Isotypes
Definition - Antigenic determinants that
characterize the classes and subclasses of
heavy chains and types and subtypes oflight chains
8/11/2019 06iso-allo-idio09 (1)
3/18
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
??
8/11/2019 06iso-allo-idio09 (1)
4/18
Immunoglobulin Isotypes
Occurrence
Importance
Ig levels
B cell tumors
Immunodeficiencies
Definition
Location
IgM (kappa)IgG1 (kappa)
CH1
CH2
CH3 + CH4
VH
VL
Isotypic variation is present in the germline of all members of a
species producing the heavy(,,,,) and light chains (Ig,) and
the V region framework
8/11/2019 06iso-allo-idio09 (1)
5/18
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
8/11/2019 06iso-allo-idio09 (1)
6/18
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
8/11/2019 06iso-allo-idio09 (1)
7/18
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
8/11/2019 06iso-allo-idio09 (1)
8/18
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
8/11/2019 06iso-allo-idio09 (1)
9/18
Immunoglobulin Allotypes
Definition
Location
Occurrence
Importance
Monitoring bone marrow grafts
Forensic medicine
Paternity testing
8/11/2019 06iso-allo-idio09 (1)
10/18
Immunoglobulin Idiotypes
Definition - Unique antigenic determinants
present on individual antibody molecules or
on molecules of identical specificity
8/11/2019 06iso-allo-idio09 (1)
11/18
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
8/11/2019 06iso-allo-idio09 (1)
12/18
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
8/11/2019 06iso-allo-idio09 (1)
13/18
Immunoglobulin Idiotypes
Definition
Location
Importance
V region marker
Regulation of immune responses
8/11/2019 06iso-allo-idio09 (1)
14/18
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.
8/11/2019 06iso-allo-idio09 (1)
15/18
Immunoglobulin Idiotypes
Definition
Location
Importance
V region marker
Regulation of immune responses
Vaccines
8/11/2019 06iso-allo-idio09 (1)
16/18
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
8/11/2019 06iso-allo-idio09 (1)
17/18
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/168/5/25238/11/2019 06iso-allo-idio09 (1)
18/18
Immunoglobulin Idiotypes
Definition
Location
Importance
V region marker
Regulation of immune responses
Vaccines
Treatment of B cell tumors (T cell)
Recommended