B and T cell receptors Flashcards
all adaptive immune Responses follow the same steps:
1- initiated by naive lymphocytes recognizing Antigen
2- Lymphocytes proliferate to increase in number
3- Some differentaite into effector cells
4- others develop into Memory cells
5- Effector cells get rid of the Antigen
6- Most of antigen-activated lymphocytes die
Phases of adaptive immune response
Regognition Phase (APCs) Activation Phase (Differentiation) Elimination Phase (humoral and cell mediated immunity) Contraction (apoptosis of lymphocytes) Memory
B and T cell receptors
B cell receptor (BCR):
- membrane Bound antibody (immunoglobulin)
- antibodies are structurally related glycoproteins produced in membrane Bound or secreted from by B lymphocytes
T cell receptor (TCR):
- strucutrally related glycoproteins produced only in membrane Bound form
they both mediate the Antigen triggered activation of B and T cells
Structure of antibodies (BCR)
- two light chains (L)
- two heavy chains (H)
- Variable (V) and constant (C) regions
- CDR (complement determining Region) (CDR1, CDR2, CDR3)
- Fc - Fragment crystalline
- Fab - Fragment Antigen binding
- Hinge Region
Two types of light Chains: κ, λ.
Five types of heavy chains: mu, δ, α, γ, ε.
Ig isotypes: IgM, IgD, IgA, IgG, IgE
Naive B cells produce: IgM, IgD
Active B cells produce: IgM, IgA, IgG, IgE
Structure of T cell receptors
- Heterodimer composed of Alpha chain and beta chain
- Variable (V) and constant (C) regions
- CDR (CDR1, CDR2, CDR3)
Comparison of BCR and TCR
- TCR is similar to Ig Fab Fragment
- TCR is only produced in membrane Bound form
Signal transduction: BCR and TCR complex
- both associate with signaling molecules that medaite the antigen-triggered activation of B and T cells
- BCR complex: BCR, Ig Alpha chain and Ig beta chain
- TCR complex: TCR, CD3, ζ chain
Properties of B and T cell receptors compared
TCR:
- ONE V and one C Domain
- three CDRs in each chain for Antigen binding
BCR:
- heavy chain –> one V Domain, three or four C Domains
- light chain –> one V Domain, one C Domain
- three CDRs in each chain
- production of secreted form
- isotope switching
- somatic mutations
Formation of BCR and TCR diversity
- are encoded by receptor genes made up of a limited number of gene Segments –> are divided in the germline Antigen receptor loci
- germline organizations of Ig and TCR genetic loci are fundamentally similar
- gene Segments are somatically recombindes in developing B and T cells –> V (D) J RECOMBINATION
TCR genes
genes Encoding the TCR Alpha chain and the TCR beta chain map to seperate loci on different chromosomes
V (D) J recombination
1) joining og on Ig VH gene Segment with one DH and one JH Segment
2) heavy chain locus: transcription of VDJ gene and splicing with Cμ RNA
3) Expression of μ chain
- functional μ chain - the first checkpoint in B cell development
Similar processes in somatic recombination:
- -> Ig light chain genes
- -> TCR Alpha and TCR beta chain genes
V (D) J recombination: junctional diversity
- diversity is also created by Radom Addition or dletion of sequences at the junctions between the Segments
- nucleotides (P sequences) may be added to asymmetrically cleaved haitpins in a templated manner
- nucleotides (N regions) may be added to the sotes of VD, VJ, DJ junctions in a nontemplated manner by the Enzyme TdT
–> These additions generate new sewuences that are not present in the germline
Maturation of B and T lymphocytes
- commitment of progentori cells to the B or T cell lineage
- Proliferation providing a large pool of cells
- Somatic recombination and Expression of Antigen receptor proteins
- Selection - Elimination of self-reactive cells
- Differentiation of B and T cells into effector cells
Maturation of B lmyphocytes
- pro-B-cells start D to J rearrangement at the Ig heavy chain locus
- Pre - B cells: VDJ recombination is completed at the Ig H chain locus
- Primary RNA transcript containing VVDJ exon and Ig C gene Exons is produced
- VDJ exon is spliced to the μ C Region Exons to generate a mature mRNA that is translated into the μ heavy chain protein
- pre-BCR is formed by Pairing μ chain with Surrogate light chains
- it delivers Survival and Proliferation Signals
- it delivers Signals for V-J recombination at light chain locus
- immature B cells: V.J occurs at Ig K locus, light chain proteins are expressed
- Heavy and light chains are then assambled into intact IgM molecules
- Mature B cells: Synthesis of μ and δ heavy chains occurs and membrane IgM and IgD are expressed
maturation of T lymphocytes
- Pro T cells CD4-CD8 start the rearrangement of the TCR beta chain genes
- Pre T cells: VDJ recombination is completed at the TCR beta chain locus
- TCR beta chain associated with the invariant pre Tα protein to form a pre TCR
- Pre TCR transduces Signals that inhibit rearragement on the other beta chain allele
- differentiatin to the stage of dual CD4 and CD8 Expression
- CD4+CD8+ T cells start VJ recombination at the TCR α locus
- Positive selection of CD4+CD8+ TCRαβ double positive thymocytes –> process is responible for tolerance to many self antigents
- TCR αβ thymocytes become eihter CD4+CD8- or Cd4-CD8+
- Naive CD4+ or CD8+ cells emigrate to peripheral lymhoid tissues
