Set: Ch. 3 - Ag Recognition by BCR and TCR

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With group: MICB 302 UBC 09
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TermDefinition
clonal_____ selection - when a mature T or B cell binds Ag, they get activated, proliferate and go on to form either memory or effector cells
negative______ selection - newly formed T and B cells that recognize self antigens get eliminated
Abs___ have to bind to Ag to neutralize it, opsonize it, or active C'
CTL____ use TCR and CD8 to bind to virus-infected cells and then kill them. Involves recog. of MHC I proteins displaying peptides derived from viral proteins
Th1___ cells use TCR and CD4 to bind to infected macrophages so they can activate them with gamma-interferon and allow macrophages to kill intracellular bacteria
disulfide_____ bonds hold H chains and L chains together and two H chains together
bindingVh and Vl combine to form the Ag _____ site of Ab
identicala single Ab has 2 identical H chains and 2 identical L chains, so 2 Ag binding sites are ________
Call _ regions for a particular type of Ig chain have identical amino acid sequence
lightthere are 2 types of _____ chains for Ab, kappa and gamma - functionally equivalent
heavythere are 5 types of ______ chains for Ab - the type of H chains determine isotype (Ig class)
C_ regions of H chain contain specific amino acid sequences that determine Ab function
complementIgM and IgG can activate ______ cascade when it binds Ags
IgM10 binding sites of secreted ___ (Ab isotype) gives its high avidity
IgMsecreted form of ___ (Ab isotype) is a pentamer
secondaryIgG is the major isotype made during _____ response
primaryIgM is the major isotype made during _____ response
IgG___ (Ab isotype) can opsonize microbes
IgA___ is the major isotype found in secretions
IgA___ (Ab isotype) is a dimer in secretions
IgE___ binds to mast cells and triggers it to release histamine -> allergic response
IgD___ (Ab isotype) is never secreted, only part of BCR
mature______ B cell has mIgM and mIgD that recognize same Ag
memory______ B cell can have mIgM, mIgG, mIgA, or mIgE on surface
VlL chains have 2 globular Ig domains - N terminal contains __ region, other on the C region
H_ chains either have 4 or 5 globular Ig domains
hinge_____ region for Ab provides flexibility that allows for Ag binding sites to bind repeating epitopes with different spacing between them
4IgG, IgA, IgD have _ globular Ig domains (Vh, Ch1, Ch2, Ch3 + flexible hinge region b/w Ch1 and Ch2)
5IgM, IgE have _ globular Ig domains ( Vh, Ch1, Ch2, Ch3, Ch4, no hinge)
secondaryglobular domains are formed by the ______ structure of H and L polypeptides
betaimmunoglobulin fold is the folding over of two ____ sheets
disulfide2 beta sheets are folded over and linked by a ______ bond to make a Beta barrel that is roughly globular in shape
50gamma, delta, alpha chains weigh ___ kDa
70mu and epsilon chains weigh ___ kDa
25L chains weigh ___ kDA
150IgG, IgD, IgA weigh ____ kDA
190IgM, IgE weigh _____ kDA
Hvthe Ag binding site is formed by the __ regions
3both the H and L chains have _ HV regions, separated by conserved regions
loopsin the 3d structure of Vh or Vl, HV regions are in ___ between the beta strands
HVthe beta strands form a conserved framework that give Vh and Vl the basic Ig domain structure while __ regions vary considerably and determine Ag-binding specificty
complementaryAbs bind epitopes whose 3d shape is ______ to that of its Ag- binding site
CDR____ - HV regions that form Ag binding site
specificAb binding is very _____ - often distinguish between closely related molecules and 1 aa change can greatly reduce affinity
CDRtypes of non-covalent bonds formed b/w aa side chain of ___ and antigen - 1) Electrostatic 2) H bonds 3) Permanent dipole - induced dipole 4) Induced dpiole - induced dipole
intactAbs recognize _____ Ags and bind epitopes exposed on surface of molecule
polyclonal_______ Abs - produced by immunizing animal, purifying Abs from serum - mixture of Abs that recognize diff. epitopes on Ag
monoclonal________ Abs - produced by fusing plasma cell with tumor cell ( = hybridoma), select single cell clones making high affinity Ab that recognizes one epitope
purifyflow cytometry, magnetic bead separation - used to identify cells or _____ cells
tissueimmunohistochemistry, immunofluorescence - used to visualize cells within _____ sections
proteinsimmunofluorescence, immunoelectron microscopy - used to visualize subcellular localization of ________
quantitateELISA - used to ________ proteins in fluids
purifyaffinity chromatography, immunoprecipitation - used to _____ proteins
detectimmunoblot - used to ____ proteins separated by SDS-page
beadsto use Ab to purify protein... (affinity chromatography) 1) Covalently couple Ab to ____ 2) Add cell lysates to Ab-coated _____. Only protein recognized by Ab is bound to ____ 3) Wash away proteins that do not bind 4) Separate bound protein from Ab (low pH - disrupt bond b/w Ag and Ab) 5) Purification
2TCR and BCR consist of _ subunits
AgTCR and BCR consist of 1) ___ binding subunit and 2) signaling subunit
mIgBCR's Ag-binding subunit is ____
chainsTCR's Ag-binding subunit is made up of TCR alpha and beta _____
IgBCR's signaling subunit is __-alpha and beta chains
CD3TCR's signaling subunit is ___ chains and TCR zeta chains
activationthe role fo the signaling subunit is to generate chemical signals inside T or B cell that leads to T and B cell _______ and proliferation
Agwhile TCR is never secreted, whole point of B cell activation is secretion of Abs with the same __ binding site as mIg on the cell that was activated
transmembranemIg is not shed from cells. secreted Abs are newly synthesized proteins that lack a _______ domain
disulfideAg binding subunit of TCR is TCR alpha and beta chains which are ______ bond linked
1unlike BCR, TCR has _ Ag-binding site per complex
zetaTCR signaling subunit consists of CD3 gamma, delta, epsilon chains and TCR ___ chains
HVlike Ig V regions, TCR Valpha and Vbeta are globular domains that consist of __ and framework regions
loopsHV regions are the _____ in Ig domains with framework regions making up the sheets that form the globular domain
BCRHV regions at tips of alpha and beta chains, and they come together to form the single antigen binding site of TCR, just like Vh and Vl join together to form Ag-binding site of an Ab or mIg portion of ___
CD3like alpha-beta T cells, gamma-delta T cells also have ___ and TCR zeta
genesgamma and delta chains for TCR are encoded by different ____ than alpha and beta chains, and also assembled by gene arrangement
MHCTCR's recognize peptides that are bound by ___ proteins on surface of APCs
linearT cells recognize ____ peptide sequences, as opposed to conformational determinants recognized by Abs
RBCMHC I is expressed on all cell types except ___
interferoncytokines released during viral infections (______ ) increased production of MHC I
alphastructure of MHC I - transmembrane ____ chain with 3 domains (___1, ___2, ___3)
groovein MHC I, alpha 1 and alpha 2 domains come together to form peptide-binding ____
apcMHC II is expressed only on professional ___ (macrophages, DC's, B cells) and on thymic epithelial cells involved in +/- selection of thymocytes
2structure of MHC II - 2 transmembrane chains, alpha and beta chains, each with _ domains
groovein MHC II, membrane-distal alpha 1 and beta 1 domains come together to form peptide-binding _____
peptideTCR binds to both MHC and _____ that is in the cleft of MHC molecule
alphaTCR docks onto ___ helices that form sides of peptide binding cleft
ratefirst, HV regions (CDR1 and CDR2 mostly) of TCR bind to MHC. ability of TCR to recognize MHC protein determines on-___ of the interaction
offsecondly, CDR 3 HV regions of both Valpha and Vbeta contact peptide in cleft of MHC. this determines the ___-rate
dissociatesif there is a poor fit (few molecular interactions b/w aa side chains of peptide and TCR CDR3s), TCR ______
CDR3if there is a good fit (many molecular interactions b/w aa side chains of peptide and TCR ____), TCR stays bound to MHC peptide
crystallizingwhich parts of TCR bind to MHC determined by co-______ a soluble form of TCR and MHC I
Ibinding of TCR to MHC _ 1) Docking of TCR to MHC _ ) Valpha binds to alpha 2 of MHC _ using CDR1 and CDR 2 2) Vbeta binds to alpha 1 of MHC _ using CDR 1 and CDR 2 3) Valpha CDR3 and Vbeta CDR3 bind to peptide
peptideVbeta of TCR actually has 4 HV regions but CDR4 does not always contact the ____
IIbinding of TCR to MHC __ 1) Valpha binds MHC __ beta1 domain, Vbeta binds MHC __ alpha 1 domain 2) Valpha and Vbeta both contact peptide 3) CDR regions bind the peptide
betaCD4 binds to aa on ___2 domain of MHC II proteins
CD8CD8 is a dimer of ____ alpha and beta
alphaCD8 alpha binds to aa on _____3 of MHC I
interfereCD4 and CD8 bind to MHC proteins away from where peptide is bound, so they do not _____ with TCR binding to MHC peptide complexes
TCD4 and CD8 ensure that the right type of _ cell is activated by MHC peptide complex
signalingCD4 and CD8 brings _______ enzymes, such as kinase Lck, close to TCR
intracellularsignaling enzymes increase ability of TCR to initiate ________ signals
Agif CD4 and CD8 is prevented from interacting with MHC proteins, need 100x more __ to get T cell activation
signalingCD4 and CD8 increase strength of TCR _______ by 100x
Tit's important for _ cells to be activated by small numbers of MHC/peptide complexes, because only a small number of MHC proteins will be presented on APC since there are many APCs with different peptides

Set Information

Terms 101
Creator neoking77
Created October 9, 2009
Group MICB 302 UBC 09
Subjects None
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  1. 70 mu and epsilon chains weigh ___ kDa - 5 misses
  2. 25 L chains weigh ___ kDA - 3 misses
  3. 50 gamma, delta, alpha chains weigh ___ kDa - 3 misses
  4. 190 IgM, IgE weigh _____ kDA - 3 misses
  5. 150 IgG, IgD, IgA weigh ____ kDA - 3 misses
  6. 2 structure of MHC II - 2 transmembrane chains, alpha and beta chains, each with _ domains - 3 misses
  7. MHC TCR's recognize peptides that are bound by ___ proteins on surface of APCs - 2 misses