Mmg 522: Scribe # 7 Antigen Recognition

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Antigen Recognition by B and T cells

How are they different based on receptors?

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For adaptive:
BCR = B cell receptor, antigen receptor complex on B lymphocytes

TCR = T cell receptor, antigen receptor complex on T lymphocytes

For innate: PRR = Pattern recognition receptor

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Immunoglobulin (Ig) supergene family

How is it named?

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Immunoglobin = antibody

All related proteins have Ig domain

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For BCR complex, name the 3 parts

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1. mIg

2. Ig(alpha)

3. Ig(beta)

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Membrane immunoglobulin is domain that recognizes and binds to antigen

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mIg

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2 transmembrane proteins that work together with mIg (antibody) to create signal transduction from the exterior of the B lymphocyte to the interior

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Ig(alpha) & Ig(beta)

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What are the 3 parts of the TCR complex?

What are their functions?

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1. TCR

2. CD3

3. Zeta

CD3 & Zeta work with TCR to create signal transduction for T lymphocyte

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CD3

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Marker for T cells since all T cells have CD3 receptors

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Regions of Ig

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C
V
Fab region
Fc region
CDR

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C region of Ig

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Constant region

Stimulates same function regardless of the antigens that are bound.

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V region of Ig

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Variable region

Ag recognizing portion of receptors and changes it from clone to clone

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Fab region of Ig

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Fab = fragment antigen binding region

Each Ab has 2 fab regions

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Fc region of Ig

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Fc = fragment crystalline region

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CDR region of Ig

What is the most variable CDR?

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CDR = complementarity determining region

Parts within the V region of both the heavy & light, give specificity for binding antigens

CDR3, located between C and V regions

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Ab can be cleaved by what enzymes?

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Papain gives 3 fragments: 2 Fab + 1 Fc

Pepsin gives 2 fragments: F(ab')2 + 1 Fc

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The isotypes of antibodies

How do they differ?

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IgM, IgD, IgG, IgA, IgE

Differ in the composition of the Fc domain

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What is the structures of antibodies?

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2 H (heavy) chains that associate with 2 L (light) chains

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Switching of the H chain of an antibody.

When an IgM can change into an IgG but will produce the same antigen-specific antibody

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Class switching

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Function of IgM

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Membrane surface receptor

Complement activation

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Function of IgG

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Opsonization

Neutralization (blocks activity of pathogen by changing biological activity of toxic proteins)

Complement activation

ADCC

Only Ab that can cross the placenta and protects fetus from mom's antibodies through FcRn receptor

Regulation of B cell, stops production of Abs

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Function of IgA

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Mucosal immunity, neonatal immunity

Found in colostrums & breast milk, gut epithelium

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Functions of IgE

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Allergic reaction, parasite infection

Works together with eosinophilic and mast cells

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Which antibody has the highest concentration in the blood?

Which antibody has the highest concentration in the body tissues?

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IgG highest in blood

IgA highest in body tissues

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Same Fab, different Fc

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Isotype

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Same Ig class from different individuals

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Allotype

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Differences of Fab region with each clone.

Unique structure produced by a single clone

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Idiotype

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Binding strength between the epitope and the antigen-binding site.

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Affinity

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How is affinity measured?

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Kd

Lower the Kd value, the higher the affinity

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Naive B cells have medium range of affinity. But once they become activated, their affinity to bind Ag increases.

Occurs only in B cells

Only a somatic mutation so won't be passed down to future B cells

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Somatic mutation

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Total binding strength based on number of different binding sites and affinities

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Avidity

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How is BCR different from TCR

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TCR & BCR are both membrane anchored but TCR doesn't secrete.

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Describe the TCR structure?

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Has 2 chains-heavey and light

Each chain has a V and C region

CDR3 is the most variable region

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Where does TCR assembly take place?

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In the thymus

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The most common type of TCR has what type of chains?

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90% of T cells have alpha/beta chains-->MHC restriction (which means they only recognize proteins when presented by MHC molecules)

Recognize peptides (adaptive immunity)

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The least common type of TCR has what type of chains?

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10% of T cells have TCR as gamma and delta chains-->not MHC restricted

Recognize phospholipids & glycolipids (innate immunity)

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Which type of receptor binds Ag with more affinity?

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BCR, has a lower Kd value

So TCR needs help from adhesion molecules to bind to epitope

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How does TCR get help to bind to epitope?

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via CD4 & CD8 receptors

TCR recognizes peptide, CD4 & CD8 recognizes MHC.

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Which type of receptor has more diversity and why?

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BCR has more diversity because it is made of 3 segments (V-variable, D-diversity, J-joining)

Whereas, TCR has less diversity since it only has V and J segments

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For BCR and TCR, only express allel from mom OR dad, not both

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Allelic exclusion

Unlike MHC which is codominant

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How are the alleles chosen for BCR and TCR?

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Random selection

Chose mom OR dad's alleles (not germline change so not passed on)

Ensures one cell, one specificity

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Once B cell is committed to one antigen specificity it won't change it's allelic exclusion, even if B cell undergoes a class switch

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Clonal selection theory