Transcript CD4 + T cells CD8 + T cells

Antigen recognition by T cells
Zheng W. Chen, M.D., Ph.D
T cell receptors (TCR) on T cells recognize antigens
TCR is a heterodimer comprised of 2
transmembrane glycoprotein chains;
TCR a chain and TCR b chain.
ab TCR heterodimers are very similar
in structure to a Fab fragment of
immunoglobulin, bearing V, (D), J, C
segments.
A majority of T cells express ab TCR
heterodimers; a minority of T cells
express another type of TCR, gd TCR
heterodimers.
CDR loops of TCR form the antigenbinding sites.
Theoretically, each T cell expresses a
unique TCR in terms of VDJ sequences.
T cell receptor ab heterodimers
TCR CDR loops form the antigen-binding sites
TCR recognize antigen peptide presented by a MHC molecule

TCR recognition of antigen differs
from antibody recognition of antigen
(TCR cannot bind directly to an
antigen peptide).

Ag peptide must be presented by a
corresponding MHC molecule
before TCR can recognize.

TCR interact with the peptide-MHC
complex (ligand) by making contact
with both the antigen peptide and
the MHC (“Dual recognition”).
Class I is comprised of one transmembrane glycoprotein (a chain) and a b2microglobulin; Class II are dimmers of a and b transmembrane glycoproteins
CD4 T cell recognize antigen peptides bound to MHC class II
molecules; CD8 T cells recognize
antigen peptides bound to MHC class I molecules.
Historically, T cell (TCR) recognition of antigen peptides were
characterized by antigen peptide stimulation assays in culture:
CD4 T cells
APC
+ specific Ag peptide
CD8 T cells
+ specific Ag peptide
(target cells) APC
Interleukin 2 (IL-2)
or Interferon g (IFN-g)
cytotoxic killing of target cells
or production of IFN-g
Why CD4 T cells recognize peptide/MHC class II and CD8 T cells see peptide/MHC class I ?
CD4+ T cells
CD8+ T cells
Antigen presenting cells (APC) and expression of MHC class I and II molecules
Professional APC: macraphages/monocytes/Langerhams cells; dendritic cells, B cells,
express both MHC class II and I.
In general, all tissue cells can express Class I; but not Class II (endothelial cells can express both).
Class I molecules bind short peptides of 8-10 amino acids by both
ends (binding sites for anchor residues of a given peptide).
MHC Class II molecules bind 12-15
AA or longer peptides
TCR binds to the MHC:peptide complex
New studies from my lab and others have shown that human and
higher primate gd T cells can recognize nonpeptide phosphoantigen
from mycobacteria (shen et al, Science 2002)
ab T cells
APC
gd T cells
presenting cells
MHC
???
Ag presentation
peptide
phosphoAg
ab TCR
gd TCR
Phosphoantigen-specific gd T cells expressing Vg2Vd2 TCR can
undergo major clonal expansion in mycobacterial infection.
(Shen et al, Science;
Chen et al, Trends Immunol, 2003).
Week 0
Week 3
Anti-Vd2-PE
0.6
0.3
0.4
0.3
Anti-Vg2-FITC
23.4
0.6