Genetics in the Generation of Antibody Diversity

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Genetics in the Generation of Antibody Diversity

• Folder Title AbGenes
• Filename AbGenesNoTP

Updated September 17, 2012
GeneTitl
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• Questions About B-Cell Responses
• Biochemical Questions
• How can Immunoglobulins recognize so many
  different epitopes?
• What does an antibody protein look like?
• How do specific antibodies work as proteins
  binding specific antigenic determinants?

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Representation of Sequence Comparisons Among
Light Chains from Antibodies with Three Different
Antigen Specificities
H3N-Ser-Val-Ile-Thr-Gly-Gly-Tyr-Ala...
Thr-Glu-Ala-Val-Tyr-Ser-Met-COO- H3N-Ser-Ile-Met-T
hr-Arg-Leu-Tyr-Gly..Thr-Glu-Ala-Val-Tyr-Ser-Met-CO
O- H3N-Thr-Gly-Gly-Thr-Lys-Leu-Tyr-Ile..Thr-Glu-Al
a-Val-Tyr-Ser-Met-COO- Variable Amino Terminal
Half Conserved Carboxyl Terminal
Half (Positions 1 to 107) (Positions 108 - 214)
LiteComp
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See Figure 4-6, Kuby 6th Edition p. 85
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(No Transcript)
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• Questions About B-Cell Responses
• Biochemical Questions
• How can Immunoglobulins recognize so many
  different epitopes?
• What does an antibody protein look like?
• How do specific antibodies work as proteins
  binding specific antigenic determinants?
• Genetic Question
• How can this diversity of structure leading to
  enormous diversity of function be coded and
  controlled by a very limited host genome?

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Problems for Genetics in Generating Antibody
Sequence Diversity

• Vast Sequence Diversity-
• Encoded by Very Limit Genome
• Heavy and Light Chain Sequence Variations-
• Almost Exclusively in only one region
• Exactly the same V-region sequences-
• End up on different C-region Isotypes

GenQuest
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Myeloma Cell DNA
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Myeloma Cell Conclusions
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Embryonic Mouse Cell DNA
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Immunology and Phone Numbers

• 315-443-1870
• 212-345-1775
• 478-367-8903
• 537-503-2078
• 409-159-6309
• 610-970-3970
• 934-620-8122
• 909-603-7023
• 800-620-6021
• 704-590-5307
• 703-725-0153
• 207-502-6671
• 435-431-0890
• 412-830-0048
• 740-592-1954
• 307-620-4450
• 490-501-5672
• 601-909-7002
• 554-891-7712

Phones
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Immunology and Phone Numbers

• -443-1870
• -345-1775
• -367-8903
• -503-2078
• -159-6309
• -970-3970
• -620-8122
• -603-7023
• -620-6021
• -590-5307
• -725-0153
• -502-6671
• -431-0890
• -830-0048
• -592-1954
• -620-4450
• -501-5672
• -909-7002
• -891-7712

315- 212- 478- 537- 409- 610- 934- 909- 800- 704-
703- 207- 435- 412- 740- 307- 490- 601- 554- 335-
SplicePhones
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Immunology and Phone Numbers

• -1870
• -1775
• -8903
• -2078
• -6309
• -3970
• -8122
• -7023
• -6021
• -5307
• -0153
• -6671
• -0890
• -0048
• -1954
• -4450
• -5672
• -7002
• -7712

315- 212- 478- 537- 409- 610- 934- 909- 800- 704-
703- 207- 435- 412- 740- 307- 490- 601- 554- 335-
-443- -345- -367- -503- -159- -970- -620- -603- -6
20- -590- -725- -502- -431- -830- -592- -620- -501
- -909- -891- -592-
SplicePhones2
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Kappa Chain DNA Vks
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Kappa Chain K-J- C
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Complete Kappa Chain
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Heavy Chain Dna VHs, C-Genes
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Heavy Chain DNA All C-Genes
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Complete Heavy Chain
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Please put away all notes and devices other than
your XR transmitter. No consulting is permitted.
This is a graded response question.
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From Kuby Immunology, 4th Ed. Upper Half of
Table Human Data Lower Half (not shown) Mouse
Data
Additional sequence diversity estimated at
several orders of magnitude (i.e. perhaps
1000-fold) is generated by junctional
flexibility, P-region nucleotide addition,
N-region nucleotide addition, and somatic
hypermutation. This allows for an estimated 100
million to a billion different possible antibody
seuquences in humans.
AbDivers
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On a scale of 5 to 1 rate todays AbGenes
Presentation5. Too slow. Get moving4. No
problem.3. About right. I can figure out what I
missed.2. Too fast1. Im lost!(This is
anonymous. We wont know who you are.)
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Save Session with Participant List
Responses. Close Session. Reset to Anonymous
Polling Open New Session for Anonymous Slide on
Scope and Pace of the course so far.
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This question will be set to anonymous so no one
will know what any specific student says. For
the first 10 classes the pace of the course is

1. Too slow. We need to move faster and cover more
   about Immunology.
2. About right. I can keep up Ok but it is a
   challenge.
3. Way too fast. Slow down! Well figure out later
   what you dont get to cover in class.

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I certify that I am here

1. True

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B-Cell Differenatiation