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Immunoglobulins

Chapter:
Nomenclature
Author(s):

Harriet S. Meyer

Immunoglobulins

  • … the antibody in serum is a mixture of perhaps
  • 100 million slightly different types of molecule…
  •  J. H. L. Playfair and B. M. Chain41(p38)
  • Plasma cells can release up to 2000 antibody mole-
  • cules per second …
  •  J. H. L. Playfair and B. M. Chain41(p43)
  • You are the antibody.
  •  Smash Mouth

Immunoglobulins are the glycoproteins that constitute antibodies. They were first recognized by serum electrophoresis and, because they were localized to the electrophoretic gamma zone, were originally referred to as γ-globulins.42-47

The term immunoglobulin and terminology for immunoglobulin classes were put forth in the 1960s.48-53 The use of the abbreviation Ig (pronounced [eye-gee]54) in preference to γ was suggested to avoid confusion with the IgG heavy chain, γ55 (see the “Heavy Chains” section below). The class of immunoglobulin molecules most abundant in serum was named IgG, the G deriving from the electrophoretic gamma mobility. The M in IgM originates in an earlier designation as a macroglobulin.

The 5 classes of immunoglobulins, from most to least abundant, are as follows:

Class

Origin of Name48,54

IgG

gamma electrophoretic mobility

IgA

from β2A-globulin, later α-immunoglobulin

IgM

macroglobulin

IgD

“process of elimination”54(p66): B reserved for mice, C had no Greek equivalent

IgE

E-reactive antibody associated with erythema of allergy

Each can be found either on a cell surface (where it serves as an antigen receptor) or in tissue fluids such as blood (where it serves as a protective antibody).

Figure 7 shows schematically the basic structural unit of all immunoglobulin molecules, including many components defined herein. An immunoglobulin can be composed of 1 such unit (monomer) or more.

Figure 7. Basic structural unit of immunoglobulin molecules. Adapted from Haynes and Fauci by permission of The McGraw-Hill Companies.56

Enzyme cleavage and antibody engineering result in fragments of the immunoglobulin molecule with specific names. Expansion of these terms is not necessary:

Fab

antigen-binding fragment

Fab′

Fab with part of hinge

F(ab′)2

2 linked Fab′ fragments

Fabc

Fb

Fc

crystallizable fragment

F′c

pFc′

Fd

Fv

variable part of Fab

scFv

single-chain Fv

Each immunoglobulin monomer contains 2 heavy chains and 2 light chains, abbreviated as follows:

H

L

Each H chain and L chain in turn contains both constant and variable regions, abbreviated as follows:

C

V

Regions of the Ig molecule may be indicated as follows:

VH

variable region of heavy chain

VL

variable region of light chain

CH

constant region of heavy chain

CL

constant region of light chain

Immunoglobulins have 3 or 4 CH domains, depending on isotype, abbreviated as follows:

CH1

CH2

CH3

CH4

Heavy Chains.

The type of heavy chain identifies the class (isotype) of immunoglobulin. Heavy chains are named with the Greek letter that corresponds to the class of immunoglobulin:

Heavy-Chain Name

Immunoglobulin Class

γ

IgG

α

IgA

μ

IgM

δ

IgD

ε

IgE

IgG and IgA subclasses and corresponding heavy chains are as follows:

Heavy-Chain Name

Immunoglobulin Subclass

γ1

IgG1

γ2

IgG2

γ3

IgG3

γ4

IgG4

α1

IgA1

α2

IgA2

CH domains may be specified according to isotype:

Cε2 Cμ4 Cα3 Cγ3

Light Chains.

There are 2 types of light chain (named for initials of the discoverers’ surnames55):

κ

λ

Both types of light chain are associated with all 5 immunoglobulin classes; that is, an immunoglobulin molecule of any type might have κ or λ light chains (but not both types in the same molecule). In humans, there are 6 classes (isotypes) of λ chain:

λ1 λ2 λ3 λ4 λ5 λ6

CL and VL regions may be specified by light chain type, as follows:

Cκ

Cλ

Vκ

Vλ

The 3 specific hypervariable regions within the variable regions of an immunoglobulin H or L chain are known as complementarity-determining regions (CDRs) and are named as follows:

CDR1 CDR2 CDR3

Heavy- and light-chain CDRs are termed HCDR1, etc, and LCDR1, etc, respectively.

The 4 framework regions (relatively invariable regions between hypervariable regions) are designated as follows:

FR1 FR2 FR3 FR4

Ig Prefixes.

The following are examples of terms combining Ig and a single-letter prefix. It is best to expand these terms at first mention (especially those with the letters m or s, each of which has more than 1 meaning):

mIgM

monomeric IgM

mIgM

membrane-bound IgM

pIg

polymeric immunoglobulin

pIgA

polymerized IgA

pIgR

receptor for polymeric immunoglobulin

sIg

surface immunoglobulin

sIgM

surface IgM

sIgA

secretory IgA

Other Immunoglobulin Components.

The secretory forms of IgM and IgA contain an additional polypeptide, the J chain (not to be confused with the joining or J segments of the immunoglobulin gene loci; see the “Immunoglobulin Genetics” section below).

Secreted IgA also contains a secretory component, SC.

Molecular Formulas.

These indicate the number of polypeptide chains that constitute an immunoglobulin molecule:

γ2L2

IgG monomer with 2 γ chains and 2 light chains

α2L2

IgA monomer with 2 α chains and 2 light chains

2L2)2SCJ

IgA dimer with 4 α chains, 4 light chains, an SC, and a J chain

2L2)5

IgM pentamer with 10 μ chains and 10 light chains

2L2)5J

IgM pentamer with 10 μ chains, 10 light chains, and a J chain

δ2κ2

IgD monomer with 2 δ chains and 2 κ light chains

ε2λ2

IgE monomer with 2 ε chains and 2 λ light chains

Fc Fragments and Fc Receptors.

Fc fragments may be specified by the heavy-chain class from which they arise57:

Fcγ1

Fcγ2

Fcγ3

Fcγ4

Fcα1

Fcα2

Fcμ

Fcδ

Fcε

Receptors for the Fc portion of immunoglobulin molecules are named as follows (cell surface marker identities, if applicable, are shown in parentheses; see 15.8.2, CD Cell Markers):

IgG receptors:

FcγRI

(CD64)

FcγRII

(CD32)

FcγRIIIA or FcγRIIIa

(CD16a)

FcγRIIIB or FcγRIIIb

(CD16b)

IgA receptor:

FcαR

(CD89)

IgM receptor:

FcμR

IgE receptors:

FcεRI

FcεRII

(CD23)

The 2 transmembrane accessory proteins associated with surface immunoglobulins on some immune cells should not be confused with terms for immunoglobulin classes or heavy chains:

Igα

(immunoglobulin-associated α; CD79a; this is not IgA or the α heavy chain)

Igβ

(immunoglobulin-associated β; CD79b)

Serologic markers associated with some heavy and light chains are indicated with roman letters and a lowercase m:

Marker

Associated Chain

G1m

γ1

G2m

γ2

G3m

γ3

A2m, A2m(1), A2m(2)58

α2

Em

ε

Km

κ

Immunoglobulin Genetics.

Each immunoglobulin light chain gene is made up of a variable (V), joining (J), and constant (C) gene segment. Each immunoglobulin heavy chain is made up of V, J, C, and D (diversity) gene segments. These segments can be referred to as follows:

VH VL JH JL CH CL DH

or, more specifically, as in the following (subscript numbers refer to the class of Ig):

Vκ Vλ Jκ Cλ2 Cμ Cα2

Subgroups (various nonallelic forms) of V, D, J, and C gene segments are specified numerically (subscript numbers refer to the class of Ig, numbers set on the line refer to the subgroup), as in:

Vκ1 Vλ3 DH1 DH3 Cα25 Cλ11 Cλ2 Jκ2 JH1

A superscript plus sign may be used to indicate expression of a specific segment, eg, by a particular B lymphocyte (see 15.8.7, Lymphocytes):

Vκ3+

The V, D, and J gene segments are brought together by DNA rearrangement. Descriptive terms for this process include the following:

V/J exon, segment, region, gene, recombination

in L-chain genes

V/D/J exon, segment, region, gene, recombination

in H-chain genes

V/(D)/J

L- and/or H-chain genes

VDJ, V/D/J, V-D-J, variable-diversity-joining

alternative terms

A leader segment (L), which codes for a leader (L) peptide, precedes each V segment. Note the following potential sources of confusion:

V, D, and J segments code for the variable (V) region of an immunoglobulin protein.

J segment does not refer to the J chain of the secretory forms of IgA and IgM (see the “Other Immunoglobulin Components” section above).

L (leader) gene segment and L (light) immunoglobulin chain are different entities. (Subscript L's, as in various terms in this section, typically refer to the light chain.)

Official Gene Terminology.

Official gene symbols for specific genes of the types discussed above are presented in the following table (see 15.6.2, Genetics, Human Gene Nomenclature). Follow author usage.

Official Gene Symbol

Immunogenetic Term

IGHA1

Cα1

IGHD

Cδ

IGHD1-1

member of DH1 subgroup

IGHE

Cε

IGHG1

Cγ1

IGHJ1

JH1

IGHV@

VH

IGHV1-2

member of VH1 subgroup

IGKC

Cκ

IGKJ@

Jκ

IGKJ2

Jκ2

IGKV@

Vκ

IGKV1-5

member of Vκ1 subgroup

IGLC@

Cλ

IGLC1

Cλ1

IGLJ@

Jλ

IGLJ1

Jλ1

IGLV@

Vλ

IGLV1-36

member of Vλ1 subgroup

Alleles.

Alleles are indicated with an asterisk and number following the gene name:

IGHA1*01

IGHD*02

IGHD1-7*01

IGHE*03

IGHG3*04

IGHM*03

IGLJ1*01

IGLV2-11*01

For more detailed molecular information about immunoglobulin genetics, consult the International ImMunoGeneTics database (http://imgt.cines.fr).59

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