MIMM 214 Lecture Notes - Lecture 27: Germinal Center, Somatic Hypermutation, Chromosome

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Lecture 28 March 17, 2017
TCR diversity
TCR
- Composed of alpha chain and beta chain
- Each has a variable and constant region
- Alpha chain locus has multiple V and J segments
- Beta chain has V, D and J segments
Combinatorial diversity of TCR
- VJ in alpha chain
- VDJ in beta chain
- Combination of alpha and beta chain
V(D)J recombination of TCR
- Similar mechanism to BCR
- V, D, and J segments flanked by RSS
- RAG-1/2 recognize these sequences
- TdT adds non coded nucleotides in the joining regions
-
- TCR has CDRs too
- 3 CDRs per chain
- These are the sites with most diversity
- CDR3 is a particularly important source of diversity
Question
- Answer: CDR3 seems to bind mostly to the antigen
o Specific mainly for antigen binding
o Other CDRs might be more responsible for MHC binding?
B cells (again)
Mature Naïve B cells
- Express transmembrane IgM and IgD
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Document Summary

Composed of alpha chain and beta chain. Alpha chain locus has multiple v and j segments. Beta chain has v, d and j segments. V, d, and j segments flanked by rss. Tdt adds non coded nucleotides in the joining regions. Cdr3 is a particularly important source of diversity. Upon activation by signal 1 & 2 some form primary focus and become plasma blasts capable of secreting ab. Note that the constant region is made up of many exons, each codes for one ig domain: constant region for igm is cmew, constant region for igd is cdelta. Secreted vs transmembrane bcrs are also due to rna splicing. One primary transcript of rna can lead to 4 options; igd or igm; secreted or transmembrane. Allelic exclusion ensures that each b cell synthesizes only one heavy and one light chain. Once a bcr is expressed on a cell surface. Other chromosome becomes methylated and inaccessible to transcription machinery.

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