Farshid Yeganeh PhD. Virtually any substance can be the target of an antibody response. "Beadle and Tatum in 1941 One gene-one polypeptide hypothesis“

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Presentation transcript:

Farshid Yeganeh PhD

Virtually any substance can be the target of an antibody response. "Beadle and Tatum in 1941 One gene-one polypeptide hypothesis“ Dreyer and Bennett postulated in 1965 that each antibody chain is actually encoded by at least two genes, one variable and the other constant Susumu Tonegawa (1987). Nobel Prize in Physiology or Medicine

Lymphocyte Development and Antigen Receptor Gene Rearrangement

Germline organization of human Ig loci.

Germline organization of human TCR loci.

Domains of Ig and BCR/TCR proteins

12/23 rule Recombination occurs between two segments only if one of the segments is flanked by a 12-nucleotide spacer and the other is flanked by a 23-nucleotide spacer

V(D)J recombination.

Checkpoint in lymphocyte maturation

Junctional diversity

Sequential events during V(D)J recombination

Diversity of antigen receptor genes.

Ig heavy and light chain gene recombination and expression.

Coexpression of IgM and IgD.

Ataxia telangiectasia, which is caused by mutations in the DNA -PKcs -family kinase ATM, a known DNA repair protein. In humans, mutations in RAGl or RAG2 that result in partial V(D)J recombinase activity are responsible for an inherited disorder called Omenn syndrome. Clinical view

David Vetter September 21, 1971 – February 22, 1984