Nonrandom TRGγ variable gene rearrangement in normal human T cells and T cell leukemias

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Abstract
To estimate the extent of the TRGγ variable (V) gene repertoire used in human T cell ontogeny, we have analyzed the variety of Vγ, gene rearrangements in a large series of T and non‐T acute and chronic leukemias. A limited heterogeneity of rearranged fragments was observed: only 13 types of differently rearranged fragments, four of which occurred only once, were found among 80 rearranged chromosomes. Furthermore, in the leukemic population as a whole, the frequency distribution of the most common types of rearranged Vγ, gene‐containing fragments appeared to be nonrandom (p < 0.01). Of interest is the clear preference for functional vs. nonfunctional V, genes (nonfunctional genes being those which carry frameshifts or nonsense mutations but which presumably can still rearrange due to their conserved signal sequences). We discuss the possibilities that this preference may result either from selection of the TRGγ product at some stage during T cell development or, alternatively, from an intrinsic, antigen‐independent polarity in Vγ, gene activation.