Adaptive Antigen Recognition Flashcards
___ selects clones with the appropriate receptor
Antigen
How many chains does the B cell receptor have?
4
How many chains does the T cell receptor have?
2
How many antigen binding sites does a B cell have?
Two (Bivalent)
How many antigen binding sites does a T cell have?
One (Monovalent)
What antigen type(s) can bind to a B cell receptor?
- Carbohydrate
- DNA
- Lipid
- Protein 3D conformation
- Macromolecule antigens
What antigen type(s) can bind to a T cell receptor?
Protein Peptides
What are the four chains that make-up B cell receptors?
IgM (x2) and IgD (x2)
Name of the B cell heterodimer that ensures surface expression of immunoglobulin during development and functions in signal transduction
Igα/Igβ
What is located in cytosolic signaling motifs?
ITAM
What are the two chains that make-up T cell receptors?
α/β chain heterodimer
What is the role of the CD3 complex in T cells?
- Ensures the cell surface expression of the TCR
- Where signaling occurs
- Involved in signal transduction
What is CD3?
Complex of invariant proteins
What invariant protein in the CD3 complex is the major source of signal transduction?
CDζ (zeta)
___ contains many ITAMS
CDζ (zeta)
What is the first mechanism of lymphocyte receptor diversity generation?
Combinatorial Diversification
What happens during combinatorial diversification?
V-J or V-D-J somatic recombinations (cell chooses at random VDJ and puts it together)
What is the second mechanism of lymphocyte receptor diversity generation?
Junctional Diversity
What happens during junction diversity?
Addition of nucleotides during process of D-J or V to DJ joining
What cell types undergo somatic hypermutation?
B cells only!
Immunoglobulin ___ chain in B cells contains constant regions for all Ab isotopes
Heavy
___ is the first isotype expressed as BCR because it is the first constant region on the gene.
μ (Cm), which is the isotope for IgM
Which light chain is preferentially expressed in BCRs?
κ (kappa) light chain
What are the steps in μ heavy chain production?
(1) Germline DNA undergoes D-J joining (somatic recombination)
(2) Rearranged DNA undergoes V-D-J joining (somatic recombination)
(3) Primary RNA transcript formed
(4) Transcription of RNA to mRNA
(5) Translation of mRNA
(6) Processing of glycosylation of protein
(7) Formation of mature polypeptide
(8) Assembly of Ig molecule
What are the two roles of recombination signal sequences (RSS)?
(1) provide recognition sites for recognition enzymes that cut and rejoin DNA
(2) ensure gene segments are joined in the correct order
What enzyme is responsible for recombing V, D, and J segments during Junction Diversity?
RAG-1 and RAG-2
Recombination Activating Genes
RAG genes only made by ___
Lymphocytes
What is the function of TdT (terminal deoxyribonucleotidyl transferase) in Junctional Diversity?
Catalyzes the random polymerization of nucleotides into DNA without the need for a template; creates random unique sequences between the coding joints and is major source of generation of diversity
N (Non-template) Nucleotides
added in a non-template random manner between coding joints
P (Palindromic) Nucleotides
Added to asymmetrically cleaved hairpins in a templated manner to complete unpaired nucleotides - repair enzymes
What are the steps in μ heavy chain production?
(1) V-J joining of germline DNA to form rearranged DNA
(2) Transcription of rearranged DNA
(3) Processing of primary RNA transcript
(4) Translation of mRNA
(5) Processing of polypeptide
(6) Mature polypeptide assembled into Ig molecule
What is the name of the heavy chain in TCR?
β Chain
What is the name of the light chain in TCR?
α Chain
What type of mutation can occur during Junctional Diversity?
Frameshift
What is the name of the heavy chain in BCR?
μ heavy chain
What is the second type of combinatorial diversity that occurs just before receptor is expressed on surface of cell?
Mix of maternal / paternal receptor chains are combined
i.e could have maternal heavy chain and paternal light chain, could have maternal heavy and light chain, etc
What are the stages of maturation in B and T cells?
(1) Stem Cell
(2) Pro-B or T
(3) Pre-B or T
(4) Immature B or T
(5) Mature B or T
Major events at Stem Cell stage
- Growth factor-mediated commitment
- Proliferation
Major events at Pro-Lymphocyte stage
- Initiation of antigen receptor gene rearrangement
Major events at Pre-Lymphocyte stage
- Selection of of cells that express pre-antigen receptors
Major events at Immature Lymphocyte stage
- Selection of repertoire
Major events at Lymphocyte subsets
- Maturation of functionally distinct T and B cell subsets
B Stem Cell
(1) Proliferation?
(2) RAG Expression?
(3) TdT Expression?
(4) Ig DNA, RNA
(5) Ig Expression
(6) Surface markers
(7) Anatomic site
(8) Response to antigen?
(1) Yes
(2) No
(3) No
(4) Unrecombined germline DNA
(5) None
(6) CD43+
(7) Bone marrow
(8) None
Pro-B Cell
(1) Proliferation?
(2) RAG Expression?
(3) TdT Expression?
(4) Ig DNA, RNA
(5) Ig Expression
(6) Surface markers
(7) Anatomic site
(8) Response to antigen?
(1) No
(2) Yes
(3) Yes
(4) Unrecombined germline DNA
(5) None
(6) CD43+, CD19+, CD10+
(7) Bone marrow
(8) None
Pre-B Cell
(1) Proliferation?
(2) RAG Expression?
(3) TdT Expression?
(4) Ig DNA, RNA
(5) Ig Expression
(6) Surface markers
(7) Anatomic site
(8) Response to antigen?
(1) Yes
(2) Yes
(3) No
(4) Recombined H chain gene (VDJ), μ mRNA
(5) Cytoplasmic μ and pre-B receptor associated μ
(aka surrogate light chain/μ chain), ALLELIC EXCLUSION
(6) B220, CD43+
(7) Bone marrow
(8) None
Immature B Cell
(1) Proliferation?
(2) RAG Expression?
(3) TdT Expression?
(4) Ig DNA, RNA
(5) Ig Expression
(6) Surface markers
(7) Anatomic site
(8) Response to antigen?
(1) No
(2) No
(3) No
(4) Recombined H chain gene (VDJ), κ or λ genes (VJ)
(5) Membrane IgM
(6) CD43-
(7) Periphery
(8) Negative selection (deletion), receptor editing
Mature, Naive B Cell
(1) Proliferation?
(2) RAG Expression?
(3) TdT Expression?
(4) Ig DNA, RNA
(5) Ig Expression
(6) Surface markers
(7) Anatomic site
(8) Response to antigen?
(1) No
(2) No
(3) No
(4) Alternative splicing of VDJ-C RNA (primary transcript) to form Cμ and Cδ mRNA
(5) Membrane IgM and IgD
(6) IgM^hi
(7) Periphery
(8) Activation (proliferation and differentiation)
Receptor Editing
- Occurs in developmentally arrested, immature B cell responding to self antigen
- Re-expression of RAG proteins for additional rearrangement of light chain genes
- If new light chain specificity does not react with self antigen, B cell will mature
- DOES NOT occur in T cells
What is the role of the surrogate light chain during the Pre-BCR stage?
- Invariant polypeptide that ensures the heavy chain is structurally sound, folded correctly and interacting with bone marrow stromal cells
- Signals to irreversibly inhibit rearrangement of the Ig heavy chain locus on the other chromosome - Allelic Exclusion
Allelic Exclusion
- An individual can only express one heavy chain encoded by only one of the two inherited alleles
- Ensures that every B cell will express a single receptor, thus maintaining clonal specificity
