10-19-09 Antigen Receptors of B and T cells 1.

Compare and contrast the structure of an IgG and a TCR molecule and describe a Fab and Fc fragment. IgG Basic structure: 2 identical Light (L and 2 identical !ea"# (! chains $ach Light chain has one "aria%le (&L and one constant ('L do(ain $ach !ea"# chain has one "aria%le (&! and three constant ('!1) '!2) '!* do(ains 'an %e %ro+en do,n into three frag(ents %# papain: 2 -a%: .frag(ent antigen %inding/ frag(ents containing the portion re0uired for antigen recognition ("aria%le region 1 Is co(posed of the ,hole light chain and half of the hea"# chain1 1 -c: . frag(ent cr#stalli2a%le/ frag(ent that tends to cr#stalli2e in solution1 Is co(posed onl# of the lo,er hal"es of the hea"# chain1

T'R

Basic structure: 1 alpha (3 and one %eta (4 chain $ach chain contains one "aria%le (either &3 or &4 and one constant ('3 or '4 region Rese(%les an -c frag(ent

2. Describe the immunoglobulin fold. $ach do(ain is (ade of t,o %eta-pleated sheets 5oined %# a disulfide %ond1 This structure for(s the i((unoglo%ulin fold1 6ote that i((unoglo%ulin folds are found in (an# proteins of the i((une and ner"ous s#ste() not 5ust on anti%odies) since the# function in cell-cell recognition1 3. What is the significance of h per!ariable regions" The "aria%le regions of %oth Ig and T'R contain h#per"aria%le regions co((onl# ter(ed complementarit determining regions: CDR1) CDR2) and CDR31 CDR3 is the most variable of the CDRs and contri%utes the (ost to antigen %inding1 $ach "aria%le do(ain contains all three '7Rs) and together the# function to for( the antigen-binding site1 In other ,ords) the h#per"aria%le regions allo, for the di"ersit# in anti%od# specificit# in each indi"idual1 -or e8a(ple) there are 1011 anti%od# specificities in a person) ,ith each specificit# ha"ing uni0ue AA se0uences in the antigen-%inding site1 #. Define the mechanism of $% and $D% &oining. $D% &oining occurs in heavy chains) ,here 7-9 5oining occurs first) follo,ed %# &-79 5oining1 The &79 5oining creates a gene that:s su%se0uentl# transcri%ed and translated to gi"e Ig protein1

$% &oining occurs in light chains) ,here &-9 5oining creates a continuous e8on that encodes the ,hole light chain & region1 Both processes occur "ia somatic recombination %efore B or T cells ha"e encountered antigen1 ;ignificance: 11 the different &) 7 and 9 co(%inations #ield combinatorial di!ersit 1 21 the reco(%ination of nucleotide se0uences at the junctions of &) 7) and 9 seg(ents is called &unctional di!ersit 1 9unctional di"ersit# #ields e"en (ore changes than co(%inatorial di"ersit#) ,hich is li(ited %# the nu(%er of a"aila%le &) 7 and 9 seg(ents1 The di"ersit# of '7R* is significantl# increased %# i(precise cutting<5oining and insertions<deletions at 76A at 5unctions '. (o) are antibod and TCR di!ersities generated"
11 21

'7R1) '7R2) and '7R* h#per"aria%le regions 'o(%inatorial di"ersit# and 5unctional di"ersit# in &9 and &79 5oining