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

Abstract

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.

Further evidence for a sequentially ordered activation of T cell rearranging gamma genes during T lymphocyte differentiation

“…These data provide an original description of y rear-rangements present in a unique subset of normal mature peripheral cells with a surface receptor including a TRG1encoded y chain. They are reciprocal of and consistent with those obtained studying either a/@' circulating lymphocytes ( [24], M.-P. Lefranc, unpublished results), or a variety of TcR a@' leukemias which should represent further stages in T lymphocyte differentiation [24][25][26]301. In the latter cells, there are either two TRG rearrangements in the TRG2 region or, less frequently, one rearrangement in the TRGl region and one in the TRG2 region which, in both cases, involve predominantly V, genes belonging to the first subgroup (and in particular V2 and V4).…”

Cloned CD3+ TcRα/β− TiγA− peripheral blood lymphocytes compared to the Ti γA+ counterparts: structural differences of the γ/δ receptor and functional heterogeneity

“…Alternatively, unproductive TRG2 rearrangements allow further differentiation towards alp. This view is consistent with results obtained in either circulating TcRa/gf lymphocytes [36, 371 or a variety of TcRa/pf leukemias [36,[38][39][40] which were found to possess to TRG2 rearrangements or, less frequently, one TRGl and one TRG2.…”

Presence and localization of T‐cell subsets in relation to melanocyte differentiation antigen expression and tumour regression as assessed by immunohistochemistry and molecular analysis of microdissected T cells

“…The relationship between the presence and localization of T‐cell subsets and the expression of melanocyte differentiation antigens (MDAs) was investigated by immunohistochemistry and the diversity of the CD8+ T cells in specified tumour areas of regressive melanoma lesions was assessed using laser‐assisted microdissection and a PCR‐based TCR‐gamma gene rearrangement analysis. Although TCR‐gamma genes are only expressed in gamma/delta T cells, they are rearranged in all T cells and can thus be used as a marker for clonal origin and/or cell diversity 6–8. Using a method described by Taylor et al 9, we were able to analyse the CD8+ T‐cell diversity of small (ie 5–20 cells) groups of cells isolated by laser‐assisted microdissection, since only one specific polymerase chain reaction (PCR) is needed to cover virtually all possible rearrangements and to establish clonal evolution.…”