No abstract

T lymphocytes are found not only as recirculating cells in the lymphoid system, but also as immobile cells in certain epithelia. T-cell antigen receptors (TCR) of both alpha/beta and gamma/delta-heterodimer subtypes can exhibit an extremely high degree of diversity. The diversity of alpha/beta TCRs derives from the use of a large number of variable (V) gene segments, as well as junctional diversity generated during rearrangement of these segments, whereas the diversity of gamma/delta TCRs derives largely from junctional elements, with a smaller contribution from a limited number of V gene segments. Many T cells in the epidermal and intestinal epithelia of mice express TCR composed of gamma/delta heterodimers. We demonstrate here that gamma/delta TCRs of T cells in both these tissues are restricted in V gene usage, with different elements predominating. The TCR junctional diversity of epidermal T cells, however, is extremely limited, whereas that of intestinal T cells is extremely diverse. The distinctive features of these two populations suggest that they develop or are selected differently for particular tissue-specific functions.

Fetal thymic and adult epithelial V gamma 3+ and V gamma 4+ T cells express gamma delta antigen receptors (TCR) with invariant junctions lacking N nucleotides. Using transgenic recombination substrates, we show that di- or trinucleotide repeats, either in the coding region or in P elements, have strong effects on the site of recombination. In other mice bearing a terminal deoxynucleotidyl transferase (TdT) transgene under the control of the CD2 promoter, we found that the frequency of canonical junctions was markedly reduced with a concomitant increase in in-frame noncanonical junctions with N nucleotides. Together, our results show that short homology repeats direct the site of rearrangement and thus play a critical role in the generation of gamma delta T cell receptor canonical junctions. Increased TdT activity in V gamma 3+ T cells has a inhibitory effect on junctional homogeneity in these cells.

Recombination of V-, D- and J-gene segments can generate an enormous diversity of T-cell antigen receptor (TCR) gene sequences. Although many gamma delta T cells fully exploit this diversification process, those in the epidermal and vaginal epithelium do not, predominantly expressing invariant gamma delta receptors in which the V-(D)-J junctional sequences in almost all the productive rearrangements are identical. The almost exclusive use of identical TCRs by cells in these sites is thought to reflect recognition of a stress-induced autologous antigen. To explain the prevalence of the invariant junctional sequences, it has been proposed that thymic selection operates on a population of originally diverse progenitor cells, resulting in a homogeneous repertoire. Alternatively the invariant sequences may result from biases in the recombination machinery in the fetal thymic progenitors of these cells. We report here the use of mice into which mutated TCR gamma-gene rearrangement substrates have been introduced as transgenes to demonstrate directly that the canonical TCR V gamma 3-J gamma 1 and V gamma 4-J gamma 1 sequences occur at high frequency in the absence of the possibility of selection for the protein products.

No abstract