segment_18Generation_of_Immunoglobulin_D

segment_18Generation_of_Immunoglobulin_D - Gener at ion of...

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Unformatted text preview: Gener at ion of I mmunoglobulin Diver sit y • L ear n how and wher e t he diver sit y is gener at ed in t he i mmunoglobulins expr essed by B cells. • U nder st and t he var iet y of m olecular mechanisms t hat lead t o differ ences in immunoglobulin specificit y. • L ear n t he molecular m echanisms for gener at ing m embr ane ver sus secr et ed for ms of immunoglobulin. T hen you will: • U nder st and t he r ole clonal select ion plays in t he i mmune r esponse. • W hy monoclonal ant ibodies for a single hybr idoma h ave ident ical ant igen-binding pocket s and t hus bind t he only one epit ope. • H ave a bet t er under st anding of why t he adapt ive i mmune r esponse t akes t ime t o develop. • Compr ehend t he exquisit e pat hogen-specificit y of t he adapt ive immune syst em. T he DNA sequence encoding a V r egion is assembled f r om t wo or t hr ee gene segment s. Ther e ar e mult iple v er sions of each of t hese gene segment s available. L ight chain V genes r equir e one DNA r ecombinat ion event . H eavy chain V genes r equir e t wo DNA r ecombinat ion event s. The D-J join is make fir st ; followed by t he V-DJ j oining. Possible Differ ent Combinat ions: K appa: 33x5=165 L ambda: 31x5=155 H eavy: 40x6=240x23=5520 T he r ecombinat ion is made bet ween t wo r ecombinat ion signal sequences (RSS). One RSS has an int er nal spacer r egion of 12 bases and t he ot her has a spacer of 23 bases. These cor r espond t o one and t wo t ur ns of t he DNA h elix. T he r ecombinat ion is accomplished by t he V(D)J r ecombinase, which cont ains pr ot eins encoded by t he r ecombinat ion-act ivat ing genes (RAG-1 and RAG-2) as well as component s t hat nor mally mediat ed r epair of dsDNA, bend DNA, or modify t he ends of br oken DNA st r ands (DNA ligase I V, DNA-dependent pr ot ein kinase, t he n uclease Ar t emis, and t he K u pr ot ein). A ddit ional diver sit y is gener at ed at t he sit e of j oining via addit ion of P and N n ucleot ides. A ft er nucleot ide addit ion, t he single st r ands base pair and t he gaps ar e filled in w it h t he appr opr iat e n ucleot ides. ...
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This note was uploaded on 04/27/2010 for the course MMG 451 taught by Professor Brooks during the Spring '08 term at Michigan State University.

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segment_18Generation_of_Immunoglobulin_D - Gener at ion of...

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