Genetic Control Of The Tcell Antigenic Receptor

A. Structure. The TCR is a dimer of either a and (3 chains (approximately 95%) or y and 5 chains (approximately 5%).

B. Function

1. In contrast to the monomeric IgM antigen receptor on the B-cell membrane, the TCRs do not respond to soluble antigens.

2. TCRs recognize antigenic epitopes only as peptidic fragments bound to either class I or class II HLA molecules on an antigen-presenting cell (APC) [e.g., dendritic cells, macrophages, B cells].

JOc a

VOcn

VOc2

VOc2

VCX1

...

-

JLILiLiU

Rearrangement JO

1. Germ line DNA

3. Rearranged DNA

A Translation Splicing Transcription

5. Protein

(T-cell receptor)

4. Rearranged DNA

Recombination

n

Figure 5-4. Synthesis of the human ap T-cell receptor (TCR) genes. Synthesis of the y8 chains is thought to follow a similar pattern. (1) Multiple variable (V) region genes and joining (J) region genes occur at the TCRa locus on chromosome 14- (2) Similarly, multiple V region, diversity (D) segment, and J region genes occur at the TCRp locus on chromosome 7. (3) During the rearrangement of a-chain genes, a randomly selected V gene is joined to a J gene and the exon is transcribed, combined with a constant (Cot) region gene, and translated. (4) Similarly, the (3-chain exon is formed by the random linkage of a V region gene, first to a D region gene and a ] region gene, and then to a CP gene. (Redrawn with permission from Janeway CA Jr, Travers P: Immunobiology: The Immune System in Health and Disease. New York, Garland Publishing, 1997, p 4:35.)

3. The co-receptors, CD4 and CD8, determine whether humoral immunity or cell-mediated immunity (CMI) occurs.

a. Binding of the CD4 molecule to a class II HLA molecule on the APC results in humoral immunity.

b. Binding of the CD8 molecule to a class I HLA molecule results in CMI.

4. Union of the specific TCR and co-receptor with the peptide—HLA membrane complex is associated with signal transduction into the cytoplasm by a complex of proteins. These proteins are collectively designated CD3.

C. Genetic makeup. Diversity among the TCRs is achieved through gene rearrangements similar to that of immunoglobulins (Figure 5-4). The phenomenon of allelic exclusion controls the genetic expression. Allelic exclusion occurs when only one of the parental alleles that code for the TCR is functional, rendering each T cell responsive to only a single epitope.

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