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

To estimate the extent of the TRG gamma variable (V) gene repertoire used in human T cell ontogeny, we have analyzed the variety of V gamma 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 V gamma gene-containing fragments appeared to be nonrandom (p less than 0.01). Of interest is the clear preference for functional vs. nonfunctional V gamma 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 TRG gamma product at some stage during T cell development or, alternatively, from an intrinsic, antigen-independent polarity in V gamma gene activation.