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Antigen recognition by T cells
Zheng W. Chen, M.D., Ph.D
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T cell receptors (TCR) on T cells recognize antigens
TCR is a heterodimer comprised of 2
transmembrane glycoprotein chains;
TCR chain and TCR chain.
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 TCR
heterodimers; a minority of T cells
express another type of TCR, TCR
heterodimers.
CDR loops of TCR form the antigen-
binding sites.
Theoretically, each T cell expresses a
unique TCR in terms of VDJ sequences.
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T cell receptor heterodimers
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TCR CDR loops form the antigen-binding sites
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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”).
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Class I is comprised of one transmembrane glycoprotein ( chain) and a 2- microglobulin; Class II are dimmers of and transmembrane glycoproteins
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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 + specific Ag peptide Interleukin 2 (IL-2)APC or Interferon (IFN-)
CD8 T cells + specific Ag peptide cytotoxic killing of target cells(target cells) APC or production of IFN-
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Why CD4 T cells recognize peptide/MHC class II and CD8 T cells see peptide/MHC class I ?
CD4+ T cells CD8+ T cells
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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).
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Class I molecules bind short peptides of 8-10 amino acids by both ends (binding sites for anchor residues of a given peptide).
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MHC Class II molecules bind 12-15 AA or longer peptides
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TCR binds to the MHC:peptide complex
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New studies from my lab and others have shown that human and higher primate T cells can recognize nonpeptide phosphoantigen
from mycobacteria (shen et al, Science 2002)
TCR
???
presenting cells
Ag presentation
TCR
peptide
MHC
APC
phosphoAg
???
T cells T cells
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Phosphoantigen-specific T cells expressing V2V2 TCR can undergo major clonal expansion in mycobacterial infection. (Shen et al, Science; Chen et al, Trends Immunol, 2003).
0.6 0.3
0.3
0.4 23.4
0.6
Anti-V2-FITC
Ant
i-V2
-PE
Week 0 Week 3