The mature T cells display thousands of heterodimer surface receptors known as T cell receptors (TCRs).

Based on the surface receptors T cells are differentiated into two types. They are:

(1) Alpha/beta (a/p) T cells:

The antigen receptors are made up of two transmembrane polypeptides designated alpha and beta. Like antibodies each polypeptide chain has an N terminal variable region with 3 hypervariable or complementary determining regions (CDRs).

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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.

Typically the two supervariable CDR3s bind to the peptide while the less variable CDRls and CDR2s bind to the MHC molecule.

(2) Gamma/delta (y/8) 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. They differ from their alpha/beta cousins in several ways:

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1. Their TCR is encoded by different gene segments.

2. Their TCR binds to antigens that can be (i) intact proteins (just as antibodies do) as well as a variety of other types of organic molecules (often containing phosphorus atoms). (ii) not “presented” within class I or class II histocompatibility molecules; (iii) not presented by “professional” antigen presenting cells (APCs) like dendritic cells.

3. Most of these T cells have neither CD8 nor CD4, on their surface. This makes sense because they have no need to recognize class I and class II histocompatibility molecules.

4. Gamma/Delta T cells, like alpha/beta T cells, develop in the thymus.

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However, they migrate from there into body tissues, especially epithelia (e.g., intestine, skin, lining of the vagina), and don’t recirculate between blood and lymph nodes (they represent no more than 5% of the T cells in the blood and are even rarer in lymph nodes). They encounter antigens on the surface of the epithelial cells that surround them rather than relying on the APCs found in lymph nodes.

The function of this subset of T cells is still a mystery. Since they are situated at the interfaces between the external and internal worlds, they may represent a first line of defense against invading pathogens. Their response does seem to be quicker than that of y5 T cells.

Curiously, many of the antigens to which y8 T cells respond are found not only on certain types of invaders (e.g., Mycobacterium tuberculosis, the agent of tuberculosis) but also in host cells that are under attack by pathogens.