SURFACE EXPRESSION OF FUNCTIONAL T-CELL RECEPTOR CHAINS FORMED BY INTERLOCUS RECOMBINATION ON HUMAN T-LYMPHOCYTES

Structural diversity of lymphocyte antigen receptors (the immunoglobul in [Ig] of B cells and the alpha/beta or gamma/delta T cell receptor [ TCR] of T cells) is generated through somatic rearrangements of V, D, and J gene segments. Classically, these recombination events involve g ene segments from the same Ig or TCR locus. However, occurrence of ''t rans'' rearrangements between distinct loci has also been described, a lthough in no instances was the surface expression of the correspondin g protein under normal physiological conditions demonstrated. Here we show that hybrid TCR genes generated by trans rearrangement between V gamma and (D) J beta elements are translated into functional antigen r eceptor chains, paired with TCR alpha chains. Like classical alpha/bet a T cells, cells expressing these hybrid TCR chains express either CD4 or CD8 coreceptors and are frequently alloreactive. These results hav e several implications in terms of T cell repertoire selection and rel ationships between TCR structure and specificity. First, they suggest that TCR alloreactivity is determined by the repertoire selection proc esses operating during lymphocyte development rather than by structura l features specific to V alpha V beta regions. Second, they suggest th e existence of close structural relationships between gamma/delta and alpha/beta TCR and more particularly, between V gamma and V beta regio ns. Finally, since a significant fraction of PBL (at least 1/10(4)) ex pressed hybrid TCR chains on their surface, these observations indicat e that trans rearrangements significantly contribute to the combinator ial diversification of the peripheral immune repertoire.