Evaluation of the percentage of peripheral T cells with two different T cell receptor alpha-chains and of their potential role in autoimmunity

Approximately 25% of mature T cells possess two distinct cytoplasmic T cell receptor (TCR) alpha -chains, due to productive gene rearrangements of bot h alleles. Expression of two different alpha -chains at the cell surface is a potential risk factor for development of autoimmunity. However, it has b een difficult to determine the frequency of peripheral T cells with two dif ferent alpha -chains at the surface. Our new approach is based on comparing by flow cytometry the percentage of cells that express a given V alpha -ch ain between wild-type mice and mice that are hemizygous for a disrupted Tcr a locus (Tcra+/-) and consequently unable to express two rearranged Tcra ge nes. We consistently found that similar to8% of total peripheral T cells ex press two surface alpha -chains. The importance of dual alpha -T cells in a utoimmunity was examined in a mouse model for rheumatoid arthritis, namely collagen-induced arthritis (CIA). No significant difference was observed be tween Tcra+/- mice and wild-type littermates, considering arthritis inciden ce, day of disease onset, and maximum arthritic score. We therefore conclud e that there is incomplete phenotypic allelic exclusion in TCR alpha, and t hat the presence of a significant number of potentially multireactive T cel ls does not increase the susceptibility to develop autoimmune arthritis. (C ) 2001 Academic Press.