B TCR a chain

LVa1 LVan Ja(~53) Ca

Germline

FIGURE 8-21 TCR a and p chain gene recombination and expression. The sequence of recombination and gene expression events is shown for the TCR p chain (A) and the TCR a chain (B). In the example shown in A, the variable (V) region of the rearranged TCR p chain includes the Vp1 and Dpi gene segments and the third J segment in the Jp1 cluster. The constant (C) region is encoded by the Cp1 exon. Note that at the TCR p chain locus, rearrangement begins with D-to-J joining followed by V-to-DJ joining. In humans, 14 Jp segments have been identified, and not all are shown in the figure. In the example shown in B, the V region of the TCR a chain includes the Va1 gene and the second J segment in the Ja cluster (this cluster is made up of at least 61 Ja segments in humans; not all are shown here).

FIGURE 8-21 TCR a and p chain gene recombination and expression. The sequence of recombination and gene expression events is shown for the TCR p chain (A) and the TCR a chain (B). In the example shown in A, the variable (V) region of the rearranged TCR p chain includes the Vp1 and Dpi gene segments and the third J segment in the Jp1 cluster. The constant (C) region is encoded by the Cp1 exon. Note that at the TCR p chain locus, rearrangement begins with D-to-J joining followed by V-to-DJ joining. In humans, 14 Jp segments have been identified, and not all are shown in the figure. In the example shown in B, the V region of the TCR a chain includes the Va1 gene and the second J segment in the Ja cluster (this cluster is made up of at least 61 Ja segments in humans; not all are shown here).

Double-Positive Thymocytes

At the next stage of T cell maturation, thymocytes express both CD4 and CD8 and are called double-positive thymocytes. The expression of CD4 and CD8 is essential for subsequent selection events, discussed later. The rearrangement of the TCR a chain genes and the expression of TCR ap heterodimers occur in the CD4+CD8+ doublepositive population soon after cells cross the pre-TCR checkpoint (see Figs. 8-19 and 8-20). A second wave of

Rag gene expression late in the pre-T stage promotes TCR a gene recombination. Because there are no D segments in the TCR a locus, rearrangement consists solely of the joining of V and J segments (see Fig. 8-21B). The large number of Ja segments permits multiple attempts at productive V-J joining on each chromosome, thereby increasing the probability that a functional aP TCR will be produced. In contrast to the TCR P chain locus, where production of the protein and formation of the pre-TCR

(double negative) (single positive) (double negative) (single positive)

(double negative) (single positive) (double negative) (single positive)

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