Lecture 6- VDJ

Lecture 6- VDJ - Bi114 Lecture V(D)Jrecombination,CSRandSH...

Info icon This preview shows pages 1–11. Sign up to view the full content.

View Full Document Right Arrow Icon
Bi 114 Lecture G ti f t BCR d TCR Generation of mature BCR and TCR V(D)J recombination, CSR and SH January 21, 2010 Reading: Chapter 4 (Janeway’s Immunobiology) D G Schatz Seminars in Immunology 16 (2004) 245 256 D.G. Schatz, Seminars in Immunology 16 (2004) 245–256 Cortes et al., PNAS 93 (1996) 14008 14013 Muramatsu et al., Cell 102(2000) 553 563
Image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Total number of antibody specificities available to Immunology Total number of antibody specificities available to an individual is at least 100,000,000,000 Health L k f ib di T ll h l i Biology Lack of antibodies or T cells One of the few examples of somatic recombination in mammals Evolution Rag genes only found in Jawed vertebrates, and they function much like transposons Took almost a century to figure out 1900 History Took almost a century to figure out 1900 Paul Echrlich proposed the side chain theory
Image of page 2
Innate vs adaptive immune Innate vs adaptive immune receptors Tailored antigen specific response for any given pathogen G t M Generates Memory
Image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
B i ib d Basic antibody structure: end protein product Each of the 5 isotypes are encoded b d ff h by different genes in the constant region of the heavy chain. Class switching generates isotypes from the initial IgM (or IgD)
Image of page 4
How are we able to get such a large amount of diversity from such a small amount of genetic material? The diverse specificity of the immunoglobulin repertoire is a result of 4 mechanisms •Combinatorial diversity among V regions •Junctional diversity •Co bi ato ial di e ity a o the li ht a d hea y hai •Combinatorial diversity among the light and heavy chain •Somatic hypermutation
Image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Experiment from 1976 Non lymphoid cells lymphocytic leukemia 1976: Susumu Tonagawa won the 1987 Nobel Prize for ʺ his Prize for his discovery of the genetic principle for ti f generation of antibody diversity. ʺ Somatic recombination Different DNA fragment Same DNA fragment
Image of page 6