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Recognition of Antigen By T cells: The TCR
March 23, 2009
11:00-12:00
THE POLYPEPTIDES OF THE TCR
TCR is a heterodimer
a and b chains are 40-50 kD glycoproteins
Both chains have V and C regions
The ab TCR is on most T cells
There is a second TCR that contains
gd TCRs
T cells with the gd TCR are in the
gut and skin. Job description remains
to be determined.
THE TCR IS A MEMBER OF THE Ig SUPERFAMILY
Both V and C regions form
domains like those in Ig
TCR V regions are similar in
size to Ig V regions
TCR POLYPEPTIDE GENES ARE ON TWO LOCI
The b locus has the most V genes
The g and d loci have the fewest V genes
Although both b and g have two C regions, there is no isotype switching
Not all loci have both D and J segments
TCR V REGIONS ARE FORMED FROM MULTIPLE GENE SEGMENTS
TCR gene rearrangement uses the same machinery as Ig genes
FUNCTIONAL REGIONS OF TCR POLYPEPTIDES
Each V region has 3 CDRs
C regions have 4 domains
extracellular
hinge
transmembrane
cytoplasmic
SHORT CYTOPLASMIC TAIL=
NO SIGNAL TRANSDUCTION
TCR GENERATION OF DIVERSITY IS SIMILAR TO Ig
1. Multiple V
2. Combinations of gene segments
3. Junctional diversity: TCR>>>Ig
4. Pairing of a and b or g and d
TCR EXPRESSION REQUIRES ASSOCIATION WITH OTHER PROTEINS
TCR on T cells is associated with
the CD3 complex and a non-CD3
dimer
The TCR (like Ig) is responsible
for antigen recognition
The other proteins (like Iga and Igb)
are responsible for signal transduction
The CD3 Proteins (g,d,e)
Highly homologous
All of them are on chromosome 11
All of them can be divided into 4 regions
1. N-terminal extracellular Ig domain
2. Short connecting peptide
3. Transmembrane region containing negatively
charged amino acids
4. Cytoplasmic tail
CYTOPLASMIC TAILS OF CD3 PROTEINS ARE RESPONSIBLE
FOR SIGNAL TRANSDUCTION
ITAMS: Immunoreceptor tyrosine based activation motif
Motif important for signal transduction
Present in cytoplasmic tails of other proteins involved in signaling
The non-CD3 signaling proteins: z and h
Both proteins come from a single gene
Most TCR complexes contain zz homodimers
Some TCR complexes contain zh heterodimers
Cytoplasmic tails have ITAMs
TCR AND BCR (mIg) RECOGNIZE ANTIGEN DIFFERENTLY
Binding Sites:
BCR has multiple sites
TCR has a single site
What they recognize:
BCR recognizes “free”, intact antigen
TCR recognizes processed antigen presented
in the context of MHC
ANTIGEN PROCESSING AND PRESENTATION
ANTIGEN PROCESSING is the intracellular generation of peptides
from protein
ANTIGEN PRESENTATION is the association of those peptides with
MHC on the cell membrane
MHC CLASS I
A single a chain with three domains
It is associated with a second protein, b2 microglobulin
MHC CLASS II
MHC class II is an ab heterodimer
Each chain has a peptide binding site associated with an Ig-like domain
TWO CLASSES OF T CELL
Classes of T cell are defined by expression
of CD4 and CD8 glycoproteins
CD8 cells are cytotoxic
CD4 T cells are helpers
CD4 and CD8 determine MHC class
binding
CO-RECEPTOR ASSOCIATION WITH MHC
MHC class I binds CD8
MHC class II binds CD4