Principles of Immunology T Cell Receptors 3906 Education

Principles of Immunology T Cell Receptors 3/9/06 “Education is a better safeguard of liberty than a standing army. ” Edward Everett

Word/Terms List o o o CD 3 CDR Heterodimer Homodimer ITAM TCR Complex

Study of TCRs o Early studies of Ag response n o B cells/Ab TCRs as an Ig/ Ig. T

Comparing BCRs vs. TCRs o BCRs n n o TCRs n n o Soluble Ags Non MHC restricted Membrane bound Ags MHC restricted (self) Both are Ag specific

TCR and BCR Structural Comparison o BCR n “Dimer of dimers” (two heterodimers) o o o n Two dimers of one heavy/one light Varying number of domains. For Ig. G 4 and 2 ; Ig. M 5 and 2 Constant and variable domains Bivalent for Ag binding o CDRs in Fab

TCR and BCR Structural Comparison o TCR n Heterodimer o o o n n One alpha/one beta Two domains each Constant and variable domains Monovalent for Ag Hypervariable regions in V domains

TCR Complex o o Includes the TCR plus CD 3 n n Contains six chains o One homodimer o Two different heterodimers Has many ITAMs o Function? o Significance? Essential for TCR expression and post Ag recognition signal transduction Intra membrane oppositely charged residues

Two Types of TCRs o o Predominantly alpha/beta Also see gamma/delta n n n Gamma/delta TCR cells are less discriminating Respond to phospholipid Ags May be “first responders”

TCR Genetic Diversity o TCR gene expression n o o 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 o Act as co-receptors n CD 4 o n CD 8 o n o Monomer; four domains Heterodimer; one domain each CD 2 Each accessory molecule reacts with a ligand on the APC or target cell

TCR Binding vs. BCR Binding o TCR binding with Ag n n Less specific than BCR Less tightly bound But more adhesion molecules Greater number of ITAMs