# Shorts 4
The antigen receptors on B and T lymphocytes are broadly similar in structure and
are believed to initiate signalling in similar ways. The antigen binding chains of these
receptors do not directly contact cytosolic signalling molecules, but interact with
accessory proteins which are also anchored in the plasma membrane and whose
cytoplasmic tails contain motifs known as ITAMs (Immunoreceptor Tyrosine based
Activation Motifs). ITAMs contain the following consensus sequence: YxxL/Ix6-
8YxxL/I
These motifs are found in proteins associated with a number of signalling receptors
in the immune system. When tyrosine residues in “YxxL/I” tetrapeptides are
phosphorylated, they may be recognized by specific SH2 domains (present in certain
proteins. SH2 domains or Src homology 2 domains are defined based on their
homology to an approximately 100 amino acid domain originally described in the Src
gene that encodes a very well studied non-receptor tyrosine kinase.SH2 domains
each recognize specific phosphotyrosine containing peptide motifs. Phosphorylated
ITAMs are therefore capable of recruiting molecules that contain specific SH2
domains to activated antigen receptors. Another domain commonly found in many
signalling molecules is an SH3 (Src homology 3) domain also originally described in
the Src kinase. SH3 domains are also about 100 amino acids in length and associate
specifically with proline rich stretches in proteins.
The TCR is made up of α and β chains (in αβ T cells) or γ and δ chains (in γδ T
cells). These antigen binding transmembrane polypeptides are linked to one another
by a disulfide bridge. Each heterodimer is associated with the CD3 complex made up
of integral membrane proteins which contain ITAMs in their cytoplasmic tails. The
antigen receptor on B cells is made up of membrane immunoglobulins (IgM and IgD
in naive B cells; IgG, IgA, or IgE in some activated and memory B cells) associated
with a disulfide linked heterodimer made up of two integral membrane glycoproteins,
Igα and Igβ. These latter proteins each contain an ITAM in their cytoplasmic tails.
The cytoplasmic tails of the µ and δ heavy chains contain only three amino acids
(KVK) which basically function as a “stop transfer” sequence during the process of
translocation into the ER and do not present a significant surface for the association
of these receptors with cytosolic signal transducers. The ITAMs in Igα and Igβ are
critical for signal transduction) by the B cell receptor.
Although antigen receptors may potentially initiate signals in multiple ways, the major
mechanism by which signals are generated is the activation of tyrosine
The antigen receptors on B and T lymphocytes are broadly similar in structure and
are believed to initiate signalling in similar ways. The antigen binding chains of these
receptors do not directly contact cytosolic signalling molecules, but interact with
accessory proteins which are also anchored in the plasma membrane and whose
cytoplasmic tails contain motifs known as ITAMs (Immunoreceptor Tyrosine based
Activation Motifs). ITAMs contain the following consensus sequence: YxxL/Ix6-
8YxxL/I
These motifs are found in proteins associated with a number of signalling receptors
in the immune system. When tyrosine residues in “YxxL/I” tetrapeptides are
phosphorylated, they may be recognized by specific SH2 domains (present in certain
proteins. SH2 domains or Src homology 2 domains are defined based on their
homology to an approximately 100 amino acid domain originally described in the Src
gene that encodes a very well studied non-receptor tyrosine kinase.SH2 domains
each recognize specific phosphotyrosine containing peptide motifs. Phosphorylated
ITAMs are therefore capable of recruiting molecules that contain specific SH2
domains to activated antigen receptors. Another domain commonly found in many
signalling molecules is an SH3 (Src homology 3) domain also originally described in
the Src kinase. SH3 domains are also about 100 amino acids in length and associate
specifically with proline rich stretches in proteins.
The TCR is made up of α and β chains (in αβ T cells) or γ and δ chains (in γδ T
cells). These antigen binding transmembrane polypeptides are linked to one another
by a disulfide bridge. Each heterodimer is associated with the CD3 complex made up
of integral membrane proteins which contain ITAMs in their cytoplasmic tails. The
antigen receptor on B cells is made up of membrane immunoglobulins (IgM and IgD
in naive B cells; IgG, IgA, or IgE in some activated and memory B cells) associated
with a disulfide linked heterodimer made up of two integral membrane glycoproteins,
Igα and Igβ. These latter proteins each contain an ITAM in their cytoplasmic tails.
The cytoplasmic tails of the µ and δ heavy chains contain only three amino acids
(KVK) which basically function as a “stop transfer” sequence during the process of
translocation into the ER and do not present a significant surface for the association
of these receptors with cytosolic signal transducers. The ITAMs in Igα and Igβ are
critical for signal transduction) by the B cell receptor.
Although antigen receptors may potentially initiate signals in multiple ways, the major
mechanism by which signals are generated is the activation of tyrosine
