Antigen Receptors

Both B cells and T cells have surface receptors for antigen.

Each cell has thousands of receptors of a single specificity;

that is, with a binding site for a particular epitope.

• T-cell receptors (TCRs) enable the cell to bind to and, ifadditional signals are present, to be activated by and respond to anepitope presented by another cell called the antigen-presenting cell or APC.
• B-cell receptors (BCRs) enable the cell to bind to and,if additional signals are present, to be activated by and respond to anepitope on molecules of a soluble antigen. The response ends with descendants of the B cell secreting vast numbers of a soluble form of its receptors. These are antibodies.

Antibodies

• are glycoproteins;
• are built of subunits containing
  • two identical light chains (L chains), each containing about 200 amino acids
  • two identical heavy chains (H chains), which are at least twice as long as light chains
• The first 100 or so amino acids at the N-terminal of both H and L chains vary greatly from antibody to antibody.
• These are the variable (V) regions.
  • Unless members of the same clone (and often not even then!), no twoB cells are likely to secrete antibodies with the same variable region.
  • The amino acid sequence variability in the V regions is especially pronounced in 3 hypervariable regions.
  • The tertiary structure of antibodies brings the 3 hypervariable regions of both the L and the H chains together.
  • Together they construct the antigen binding site against which the epitope fits. [View]
  • For this reason, the hypervariable regions are also called complementarity determining regions (CDRs).
• Only a few different amino acid sequences are found in the C-terminals of H and L chains.
• These are the constant (C) regions.
• Humans make
  • two different kinds of C regions for their L chains producing
    • kappa (κ) L chains
    • lambda (λ) L chains
  • five different kinds of C regions for their H chains producing
    • mu (µ) chains (the H chain of IgM antibodies)
    • gamma (γ) chains (IgG)
    • alpha (α) chains (IgA)
    • delta (δ) chains (IgD)
    • epsilon (ε) chains (IgE)
  • each of these 5 kinds of H chains seems to have no particular preference for pairing with lambda or kappa L chains

This image represents the polypeptide chain structure of a molecule of IgG.

The numbers indicate the number of amino acids (counting from the amino terminal ("N").

In the actual molecule, the chains are folded to that each cysteine is brought close to

the partner with which it forms a disulfide (S–S) bridge.

The images below (courtesy of Dr. D. R. Davies) represent the folded (tertiary) structure

of an entire L chain (right side with thin connecting lines) and the V region plus

the first third of the C region of a heavy chain (left side; darker lines).

Each circle represents the location in 3D space of an alpha carbon.

The filled circles at the top are amino acids in the hypervariable or

complementary determining regions (CDRs);

they form the site that binds the antigen.

Do try to fuse these two images into a stereoscopic (3D) view.

I find that it works best when my eyes are about 18" from the screen and

I try to relax so that my eyes are directed at a point behind the screen.

Antibody molecules have two functions to perform:

• recognize and bind to an epitope on an antigen
• trigger a useful response to the antigen

The division of labor is:

• V regions are responsible for epitope recognition
• C regions are responsible for triggering a useful response

So, V regions finger the culprit; the C regions take action.

Why 5 kinds of heavy chains?

To provide for different effector functions.

"mg/ml" gives the concentration normally found in human serum.

Note also that humans actually make four slightly different versions of IgG (and two of IgA);

in both cases, encoded by different C-region gene segments.

T-Cell Receptors for Antigen (TCRs)

alpha/beta (αβ) T cells

The antigen receptor on most T cells is made up of two transmembrane polypeptides

designated alpha and beta (thus forming a heterodimer).

Like antibodies

• each has an N-terminal variable region with 3 hypervariable or complementary determining regions (CFRs);
• the CDRs of the two chains cooperate to form a single binding site for the epitope.
• The epitope seen by T cells consists of an antigenic peptideinserted into a groove formed by a major histocompatibility complex(MHC) molecule [View]. Typically
  • the two super-variable CDR3s bind to the peptide while
  • the less variable CDR1s and CDR2s bind to the MHC molecule.

Links to more on αβ T cells:

• general discussion
• CD4⁺ subset
• CD8⁺ subset
• Helper subsets (Th1 and Th2)

gamma/delta (γδ) T cells

A small percentage of the T cells in the blood use a TCR consisting of a heterodimer

of two other types of transmembrane polypeptides: gamma and delta.

The function of this subset of T cells is still a mystery. 

Antigen Receptor Genes

Each chain of a BCR or TCR is encoded by a gene that is assembled from

separate gene segments during the differentiation of the cell.

The resulting gene is transcribed into a mRNA to be translated into one chain of the receptor.

The number of gene segments from which the variable regions are constructed is

sufficiently large that both B cells and T cells can generate as many as 10¹⁰ different

antigen-binding sites.

There is probably no epitope that could exist for which BCRs and TCRs able to bind it are

not built.

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Posted by gwlee