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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, if additional signals are present, to be activated by and respond to an epitope 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 an epitope 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.
Discussion of antigen presentation to B cells and T cells


  • 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 two B 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" (about 46 cm) 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.

If an antibody's H chains (see IgG above), are cut at its hinge region on the N-terminal side of the disulfide bonds holding the H chains together, 3 fragments are produced:

  • 2 Fab fragments ("fragment antigen-binding") and
  • 1 Fc fragment ("fragment crystalline" — because the uniformity of this region allows crystals to form while the great diversity of V regions prevents them from forming).

Why 5 kinds of heavy chains? To provide for different effector functions.

The 5 classes of antibodies
ClassH chainL chainSubunitsmg/mlNotes
IgG gamma kappa or lambda H2L2 6–13 transferred across placenta; four subclasses: IgG1-4 in humans
IgM mu kappa or lambda (H2L2)5 0.5–3 first antibodies to appear after immunization
IgA alpha kappa or lambda (H2L2)2 0.6–3 much higher concentrations in secretions; two subclasses
IgD delta kappa or lambda H2L2 <0.14 function uncertain
IgE epsilon kappa or lambda H2L2 <0.0004 binds to basophils and mast cells sensitizing them for certain allergic reactions

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

The subclasses of IgG and IgA are encoded by different C-region gene segments.


If an antibody-secreting cell becomes cancerous, it will grow into a clone secreting its single class of molecule. The disease is called multiple myeloma. See how IgG, IgM, and IgA molecules appear in the serum of these patients.

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 (CDRs);
  • 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 peptide inserted 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:

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. [More]

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 more than 107 different antigen-binding sites. There is probably no epitope that could exist for which BCRs and TCRs able to bind it are not built.

The mechanisms by which B cells and T cells generate receptors of such extraordinary diversity.
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30 April 2012