Principles of Immunology

T Cell Receptors3/9/06

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Edward Everett

Word/Terms List

CD3 CDR Heterodimer Homodimer ITAM TCR Complex

Study of TCRs

Early studies of Ag response B cells/Ab

TCRs as an Ig/ IgT

Comparing BCRs vs. TCRs

BCRs Soluble Ags Non MHC restricted

TCRs Membrane bound Ags MHC restricted (self)

Both are Ag specific

TCR and BCR Structural Comparison

BCR “Dimer of dimers” (two heterodimers)

Two dimers of one heavy/one light Varying number of domains. For IgG 4 and

2 ;IgM 5 and 2 Constant and variable domains

Bivalent for Ag binding CDRs in Fab

TCR and BCR Structural Comparison

TCR Heterodimer

One alpha/one beta Two domains each Constant and variable domains

Monovalent for Ag Hypervariable regions in V domains

TCR Complex Includes the TCR plus CD3 CD3

Contains six chains One homodimer Two different heterodimers

Has many ITAMs Function? Significance?

Essential for TCR expression and post Ag recognition signal transduction

Intra membrane oppositely charged residues

Two Types of TCRs

Predominantly alpha/beta Also see gamma/delta

Gamma/delta TCR cells are less discriminating

Respond to phospholipid Ags May be “first responders”

TCR Genetic Diversity

TCR gene expression Seen in T cells only

Alpha chain encoded by V and J segments (~ to Ig light chains)

Beta chain encoded by V, D and J segments (~ to Ig heavy chains)

Combinatorial joining occurs resulting in at least 3 million combinations

No somatic mutation contributing to diversity

TCR Accessory Molecules

Act as co-receptors CD4

Monomer; four domains CD8

Heterodimer; one domain each CD2

Each accessory molecule reacts with a ligand on the APC or target cell

TCR Binding vs. BCR Binding

TCR binding with Ag Less specific than BCR Less tightly bound But more adhesion molecules Greater number of ITAMs