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Genetic Immunoglobin
| Question | Answer |
|---|---|
| Who and in what year did the one gene one protein model of proteins become refuted? | 1965 Dreyer and Bennett |
| Who validated Dreyer and Bennett? In what year | 1976, Tonegawa & Hozumi |
| What did Tonegawa and Hozumi produce to refute the one gene one protein model? | Seperate genes for the V and C regions of Igs; Genes are rearranged during B-cell Differentiation; received the nobel prize 1987 |
| Gene segement | coding sequence for each Ig chain from multigene families |
| V gene segement | variable; 5' signal (leader peptide) |
| D gene segments | diverse |
| J gene segement | joining |
| C gene segments | constant |
| Light chains; lamda, kappa, are composed of what gene segments | V, J, C segments |
| Lambda chains have how many V, J, and C regions in humans | 30 V, 4 J, 7 C |
| Kappa chains in humans have how many V, J, C regions | 40 V, 5 J, 1 C |
| What does the order of C regions specify? | the antibody class |
| What is the sequential order of Ig expression? | C(mu)(IgM)- C(delta)(IgG)-C(epsilon)(IgE) - C(alpha)(IgA) |
| When do multiple gene segments come together to from one protein? | variable-region rearrangement occurs after the hematopeoietic stem cell has become a lymphoid cell |
| Nascent polypeptide | polypeptide with the leader sequence still attach |
| RSSs | Recombination Signal Sequencees |
| Three descriptions of RSS | recognized by recombinase; palindromic heptamer, conserved AT-rich nonamer; one turn (13 bp); two turn (23 bp) |
| V(D)J recombinases | enzymes recognized RSSs, cut DNA, and help religate it |
| one turn/two turn rule | one turn spacers can only join with two turn spacers; ensures correct order of joining |
| RAG-1 and RAG-2 | Recombination activating genes, lymphoid-specific V(D)J rearrangement genes |
| coding joint | the region were the two new gene segments have joined; there is junctional diversity in this location |
| P-region nucleotides additions | nucleotides added into the cut region of the hair pin; coding sequences is then trimmed by ssendonuclease; adding nucleotides at the palindromic sequences |
| N-region nucleotides additions | addition of up to 15 nucleotides at the cut ends of the V, D, J coding sequences of the heavy chain by enzyme terminal deoxynucleotidyl transferase |
| What can trim nucleotides from the DNA that was cut in V(D)J rearrangment in heavy chains? | endonucleases |
| what helps to contribute to antibody diversity and hypervariability? | V(D)J rearrangment, explain how |
| What can be the outcome of Ig-gene rearrangments? | Producing productive or nonproductive Ig; adding or deleting nucleotides in coding regions can lead to frameshift mutations |
| The joint of the two gene segments is or is not flexible | It is flexible |
| What is the difference in Junctional flexibility between Signal joints (RSS/RSS) and Coding joints(V,J) in Pre-B Cell lines? | Coding joints do not joint directly (lose/gain nucleotides); signal joints join direct at the 3' to 5' nucleotides there is no lose/gain rearrangment in nucleotides |
| What is the outcome of cells that do not produce in-frame heavy and light chains? | They commit apoptosis; often occurs due to addition of stop codon |
| allelic exclusion | the process of expressing rearranged heavy-chain genes from one chromosome and the rearranged light chains from one chromosome Functional B-cells must be specific for only one antigen (epitope) |
| In an allelic exclusion once a productive rearrangment occurs | the expression of that protein controls rearrangment |
| Functional mu chain signals rearrangement of what what chain? What does this prevent? | kappa chain, it prevents further rearrangment of the heavy chains |
| What does functional k chain signal for and this lead to? | kappa signals for no more light chain rearrangments; no functional kappa chain lead to lambda chain rearrangments |
| What is the order of rearrangment of the chains? | Heavy chain than light chain kappa; then light chain lambda |
| TdT | terminal deoxynucleotidyl transferase |
| What contributes to the diversity of CDR3 | Joint flexibility, P-region nucleotide addition, N-nucleotide addition |
| What is somatic hypermutation | intential increases in mutation rates of the DNA; 10^-3 basepair/generation 1000x greater than normal; normal is 10^-8 |
| Somatic hypermutation primarily what type of substitutions and where does it mostly occur? | nucleotide substitions targeted to 1500 bp of rearranged V regions; looking for sequence motiff and palindromic motiffs; includes the entire VJ or VDJ segments |
| In somatic hypermutation; what is affinity maturation | the process of antigen affinity increasing as a population of B-cells mature; mutations that increase infnity are selected for |
| Where are somatic hypermutations clustered? | CDRs of Vheavy and Vlight, method antigen binding site being altered after V(D)J rearrangement |
| How does heavy/light chain combination provide antigen binding diversity? | Each chain provides half an antigen binding site; 6624 heavy chains; 375 light chains so together they produce 2,484,000 combinations |
| What is class switching? | the rearrangement of the heavy chain VDJ unit to combine with any heavy chain C segment |
| What does class switching require? | Switch regions(much larger than RSSs); switch recombinase, cytokine signals, AID |
| Where do switch regions exist? | between each heavy chain region except C delta |
| AID | acitivation induced citidine deaminase |
| Functions of AID | deaminates cytosines, converts them to uracil in both RNA and DNA |
| What can lead to B-cell lymphoma | essential somatic hypermutation and class switching |
| characteristics of the expression of Ig Genes | membrane of secreted, b-cells can express different classes of antibody at the same time, no switch between mu region and delta region |
| How are the long chains of membrane bound antibodies are different than secreted antibodies different? | M- region that incodes amino acids that are hydrophobic |
| Where are secreted/membrane bound Ig proteins synthesized | In the RER, signal/leader peptide that watches were to begin |
| How is the production of Ig controlled either quantity or improperly folded proteins? | chaperone BiP binds to Ig remains in ER, dissassembled, exported to cytosol, ubiquination, proteasome degredation |
Created by:
jdonovan
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