DEVELOPMENT AND PHYSIOLOGIE OF A SUB-POPULATION OF T CELLS, THE gd T CELLS

Allelic and isotypic exclusion of TCRg genes (L. Boucontet and P. Pereira)

Most lymphocytes express only one antigen receptor at cell surface. This phenomenon, known as allelic exclusion, results from different mechanisms depending of the locus involved. We have developed an experimental system allowing the analyses of TCRg and TCRd gene rearrangements in progenies of gd T cell with high efficiency and analyzed close to 250 gd thymocyte clones selected by their expression of different TCRg chains at the cell surface. Several important conclusions emerge from these analyses. First, our results suggest a hierarchy in the probabilities at which different Jg and Vg gene segments are engaged in a recombination process. Second, although an important fraction of gd T cells contain two or more functionally rearranged TCRg chains, only one of these TCRg chains is expressed at detectable levels at the cell surface. This is the result of at least two different phenomena. On one hand, several TCRg chains only pair with a restricted number of TCRd chains. On the other hand, different TCRg chains compete unequally for the same TCRd chain or for other components of the TCR-CD3 complex with Vg1 chains dominating over Vg4 chain and both dominating over Vg2 chains. Third, less than 1 % of mature gd thymocytes contain both alleles of the same TCRg chain functionally rearranged, suggesting that both alleles are not open to recombinase action at the same time. Fourth, precursors of gd T cells do not attempt to rearrange all Jg segments.

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