Lecture 12: Immunoglobulin Diversity Flashcards
Recall isotype, allotype, and idiotype.
- Isotype
- class or sub-class of Ig
- Allotype
- existence of alleles in Ig loci
- e.g. IgG1 will have minor differences between different individuals
- Allotypes are used for paternity testing
- existence of alleles in Ig loci
- Idiotype
- variation in variable region
- Individuals may have up to 107 different idiotypes
How do you determine numerically variability in Ig?
Variability (V) = (no. of diff. aa at a given position)/(frequency of most common aa at the position)
Recall the basic composition of a gene.
Describe the process of somatic diversification of Ig gene.
Ig genes are rearranged in the progenitors of antibody-producing cells. Rearrangement occurs during B cell maturation from immature pre-B cell to mature B cell. Rearranged segment generate:
- complete Ig H+L chain genes
- unique Ig H+L protein sequences
Unique genes generate unique idiotype or specificity for each B cell.
Recall the gene segments of the H and L chain.
Complete genes that encode a variable region are generated by the _______________________ of separate gene segments.
somatic recombination
Recall the diagram of light chain rearrangement.
Recall the Kabat-Wu Plot for light chains after gene rearrangement.
Recall the diagram of heavy chain gene rearrangement.
Recall the Kabat-Wu Plot for heavy chains after gene rearrangement.
Rearrangement of germline V, D, and J gene segments is guided by _________________. Joining follows the ________.
RSSes in the Ig genes form loops which are removed by the _________________.
Describe the V(D)J recombinase enzyme complex.
The V(D)J recombinase enzyme complex is made up of both lymphocyte-specific and ubiquitous DNA-modifying factors to facilitate the recombination of V, D, and J gene segments.
The key enzymes involved are recombination activating genes 1 and 2 (RAG), terminal deoxynucleotidyl transferase (TdT), ligases, and Artemis nuclease
Mention the key roles of enzymes in the V(D)J recombinase enzyme complex.
Recall how N regions contribute to the diversity of Ig.
There is “imprecise” joining of the V => D, D => J gene segments because of deletion and insertions of nucleotides by the TdT enzyme. N-regions contribute to diversity (i.e. almost any sequence is possible in the N-regions); but may lead to failure of rearrangement (e.g. insertion of stop codons or frameshifts)
Recall the overview of the joining stage of the Ig gene rearrangement process.
What contributes to the diversity of the third hypervariable region.
Recall the sources of Ig diversity.
How do V segments come into proximity with other J or DJ segments further along the gene?
