Antigen Recognition in the Adaptive Immune System

Comprehensive practice questions covering antigen receptor structure, heavy and light chain genetics, lymphocyte maturation checkpoints, and diversity mechanisms in the adaptive immune system.

What are the two specific regions that an antigen receptor consists of to handle recognition and effector function?

The variable region provides for antigen recognition, while the effector function region is relatively conserved among clones.

What are the components of an antibody monomer?

An antibody monomer comprises two identical heavy ($H$) chains and two identical light ($L$) chains, held together by disulfide bonds.

Which part of the antibody determines its class or isotype?

The heavy chains ($HCs$) determine the class or isotype ($IgG$, $IgM$, $IgA$, $IgD$, or $IgE$).

What are the two types of light chains found in antibodies?

The light chains come in two types: kappa ($\kappa$) and lambda ($\lambda$).

What is the function of the Fab (Fragment, antigen-binding)?

It contains highly variable amino acid sequences called Complementarity Determining Regions ($CDRs$) that serve as the specific binding site for a target antigen.

What is the role of the Fc (Fragment, crystallizable) region of the heavy chain?

It interacts with host immune cells, such as macrophages, and complement proteins to clear the pathogen.

How many hypervariable regions ($CDRs$) are contained in each $VH$ and $VL$ chain?

Each chain contains three $CDRs$, for a total of six $CDRs$ that determine antigen specificity.

Which hypervariable region is considered the most variable and where is it located?

$CDR3$ is the most variable and is located at the junction of the $V$ and $C$ regions.

What are the less variable stretches of the variable region located between hypervariable regions called?

Framework regions ($FR$); there are $4$ framework regions in each light chain and each heavy chain.

What are the five main classes of human immunoglobulins and their corresponding heavy chain Greek letters?

The classes are $IgM$ ($\mu$), $IgD$ ($\delta$), $IgG$ ($\gamma$), $IgE$ ($\varepsilon$), and $IgA$ ($\alpha$).

What is the definition of an epitope (antigen determinant)?

An epitope is the specific structure recognized by an antibody.

What is the difference between a linear epitope and a conformational epitope?

A linear (continuous) epitope is a single segment of a polypeptide chain, while a conformational (discontinuous) epitope is composed of amino acids from different parts of the chain brought together by protein folding.

How are affinity and avidity distinguished in antibody binding?

Affinity is the strength with which one antigen-binding site binds to one epitope, while avidity is the overall strength of binding of a multivalent antibody to a multivalent antigen.

How are monoclonal antibodies produced in a laboratory setting?

They are produced by the somatic fusion of splenocytes to a myeloma cell line partner to create hybridomas.

What are the components of the membrane-bound $T$ cell receptor ($TCR$)?

The $TCR$ is a heterodimeric protein composed of an $\alpha$ chain and a $\beta$ chain, each containing one variable ($V$) and one constant ($C$) region.

Which invariant signaling proteins associate with the $TCR$?

The $TCR$ associates with the $CD3$ complex and $\zeta$.

What is a major difference between the antigen recognition of antibodies versus T cell receptors ($TCRs$)?

Antibodies can bind many different types of chemical structures with high affinity, whereas $TCRs$ only recognize peptide-$MHC$ complexes with relatively low affinity.

According to the clonal hypothesis, how many lymphocytes with distinct specificities are predicted to exist in an individual?

About $10^{7}$ to $10^{9}$ lymphocytes.

Where does lymphopoiesis primarily take place for $B$ cells and $T$ cells?

Bone marrow for most $B$ cells and the thymus for most $T$ cells.

What are the four successive steps in the maturation of lymphocytes from stem cells?

Commitment of hematopoietic progenitors to a lineage, proliferation, rearrangement and expression of antigen receptor genes, and selection events.

What occurs during the expression of an $Ig$ heavy chain gene?

Two recombination events occur: first $D-J$ joining, followed by joining of a $V$ region to the $DJ$ complex.

What allows for the simultaneous expression of both $IgM$ and $IgD$ as B-cell receptors ($BCRs$)?

Alternative splicing of the primary RNA transcript.

Which proteins compose the lymphoid-specific $V(D)J$ recombinase?

Recombination-activating gene $1$ and $2$ ($RAG-1$ and $RAG-2$) proteins.

To which conserved sequences do $RAG$ proteins bind during somatic recombination?

They bind to heptamer ($7$) and nonamer ($9$) recombination sequences, separated by $12$ and $23-bp$ spacers.

Which enzyme assists $RAG-1$ and $RAG-2$ in the cleavage of DNA during recombination?

The enzyme called $ARTEMIS$.

What is combinatorial diversity in the context of antigen receptors?

Diversity produced by using different combinations of $V$, $D$, and $J$ gene segments in different clones of lymphocytes.

What are the three mechanisms that generate junctional diversity?

Random addition of N nucleotides by Terminal deoxyribonucleotidly transferase ($TdT$), addition of P-nucleotides (palindromic), and removal of nucleotides by exonucleases.

What is allelic exclusion and why is it important for $B$ cells?

It is the process where a cell expresses only one of two inherited alleles, ensuring that the $B$ cell produces $BCRs$ of a single specificity for high avidity binding.

What is the composition of the pre-B cell receptor?

It is made up of a heavy chain ($HC$) and a surrogate light chain.

In light chain gene rearrangement, which locus is typically rearranged first?

The kappa ($\kappa$) locus is usually rearranged before the lambda ($\lambda$) locus.

What is the first checkpoint in $B$ cell development?

It determines if a successful rearrangement of the heavy chain ($HC$) $Ig$ gene segments occurred and formed a pre-B cell receptor.

What happens if a $B$ cell fails the second checkpoint regarding light chain rearrangement?

No functional $IgM$ $BCR$ can be expressed at the cell surface, and the cell dies by apoptosis.

What are the three possible fates for immature $B$ cells that recognize self-antigens with high affinity in the bone marrow?

They are deleted (apoptosis), change specificity (receptor editing), or enter a state of hyporesponsiveness (anergy).

What is the role of the Autoimmune regulator ($AIRE$) in the thymus?

It induces the expression of tissue-specific genes in thymic epithelial cells to make host tissue-specific (self) peptides available for presentation to maturing $T$ cells.

What does the first checkpoint in T cell maturation test for?

The presence of a functional $\beta$ chain that can associate with the surrogate $\alpha$ chain to form a pre-TCR.

What is tested during the second checkpoint of T cell maturation?

The presence of a functional $\alpha$ chain that associates with the $\beta$ chain to form the complete $TCR$.

Which transcription factor controls the development of $B$ cells?

Pax-5.

Which transcription factor controls the development of $T$ cells?

Notch-1.

What is the purpose of positive selection in double-positive $T$ cells?

To ensure that the type of $MHC$ recognized matches the coreceptor preserved, resulting in $CD8+$ class I $MHC$ restricted or $CD4+$ class II $MHC$ restricted cells.

What is negative selection in the thymus?

The elimination of immature $T$ cells whose receptors recognize self-peptide:self-MHC complexes too strongly to prevent autoimmunity.