I&d Generation Of Antigen Receptor Diversity

Front 1

Heterodimers consisting of disulphide-linked alpha-beta or gamma-delta polypeptide chains

Back 1

TCRs

Front 2

In antibodies, the two light chains are disulphide-linked to eachother T/F

Back 2

F - the heavy chains are. The light chains are disulphide bonded to the heavy chains as well.

Front 3

Gene recombination is used to create variable region diversity for antigen recognition T/F

Back 3

T

Front 4

How is diversity of antibodies created?

Back 4

Recombination of 3 or 4 different gene segments

Front 5

What encodes the constant region of an antibody?

Back 5

The 'constant region gene segment'

Front 6

What encodes the variable region of the antibody?

Back 6

Three (for heavy chains) or two (for light chains) 'gene segments'

Front 7

What are the different gene segments?

Back 7

Variable (V), diversity (D) (not present for light chains) and joining (J) gene segments

Front 8

Diversity (D) segments are present for light chains T/F

Back 8

False

Front 9

What are the three sets of gene segments coding for antibody, and on what chromosome are they found?

Back 9

Set for:
Heavy chains (chromosome 14)
Kappa chains (chromosome 2)
Lambda chains (chromosome 22)

Front 10

The gene segments for heay chains are found on which chromosome?

Back 10

Chromosome 14

Front 11

The gene segments for kappa light chains are found on which chromosome?

Back 11

Chromosome 2

Front 12

The gene segments for lambda light chains are found on which chromosome?

Back 12

Chromosome 22

Front 13

The V, D and J gene-segments are inherited from generation to generation through the germ cells T/F

Back 13

T

Front 14

How many V gene segments are available for use by the heavy chain and light chain?

Back 14

40 (but it varies slightly between individuals)

Front 15

In B-cells (ONLY!) how many of the immunoglobulin V genes will be chosen at random to undergo recombination with one J or D gene segments?

Back 15

One!

Front 16

In all other cells in the body, the antibody genes remain in the germ line (non-recombined) configuration, apart from...

Back 16

...one of the Ig V genes from a B cell

Front 17

In what cells ONLY do TCR genes undergo recombination?

Back 17

T-cells

Front 18

Which enzyme mediates the recombination process in B-cells?

Back 18

Recombinase enzymes

Front 19

Recombinase enzymes are the products of the recombination activating genes...

Back 19

RAG-1 and RAG-2

Front 20

What stretch of nucleotides do the RAG enzymes recognise?

Back 20

The recombination signal sequence (RSS), which flanks the V, D and J gene segments

Front 21

The recombination signal sequence (RSS)

Back 21

Stretch of nucleotides that flank the V, D and J gene segments which RAG enzymes recognise

Front 22

Consists of a highly conserved heptamer (7 nucleotide) - nonamer (9 nucleotide) sequences separated by non-conserved 12 or 23 base pair spacers

Back 22

What RSS consists of

Front 23

What does the '12-23' rule ensure?

Back 23

That the precise number of requred segments are recombined (e.g. for one Ig heavy chain, only one V, only one D and only one J)

Front 24

Give examples of a genetic diversification mechanism that further adds diversity to the antibody.

Back 24

Imprecisions in the splice junctions between V, D and J

Insertion of nucleotides at the junctions by an enzyme called 'terminal deoxynucleotidyl transferase [TdT]

Somatic hypermutation

Front 25

What are the regions in an antibody that show exceptional variability?

Back 25

The 'complementarity determining regions' (CDR)

Front 26

How many CDRs are on the heavy chain?

Back 26

3

Front 27

How many CDRs are on the light chain?

Back 27

3

Front 28

Which part of the antibody actually recognises the antigen?

Back 28

The complementarity determining regions (CDR)

Front 29

Which gene segment contains sequences encoding CDR1 and CDR2?

Back 29

The V gene segment

Front 30

What gene segment encodes the CDR3 sequence?

Back 30

A combination of V, D and J (or V and J for light chain) gene segments

Front 31

Which, out of CDR1,2 and 3, is more diverse? Why?

Back 31

Three is, because it is eincoded by a combination of V, D an J (or V and J for light chains), whilst 1 and 2 are encoded by V only

Front 32

IgM and IgD are co-expressed on naive B-cells T/F

Back 32

T

Front 33

The constant region genes define the _____ of the antibody

Back 33

Class (or 'isotype')

Front 34

What defines the class (isotype) of the antibody?

Back 34

The constant region genes

Front 35

IgM and IgD have the same variable region on naive B-cells T/F

Back 35

T

Front 36

How is the ability of naive B-cells to co-express two different classes of antibody brought about?

Back 36

By the production of a long, primary RNA transcript which includes the VDJ region and the constant region for both IgM (C-mu) and IgD (C-delta)

Front 37

What happens to the transcripts when naive B-cells are activated?

Back 37

The transcripts are processed from long, primary RNA into mRNA from which the C-delta gene is spliced out in some, whilst others have the C-mu spliced out