Evaluation of the percentage of peripheral T cells with two different T cell receptor α-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 both alleles. Expression of two different alpha -chains at the cell surface is a potential risk factor for development of autoimmunity. However, it has been difficult to determine the frequency of peripheral T cells with two different 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 -chain between wild-type mice and mice that are hemizygous for a disrupted Tcra locus (Tcra+/-) and consequently unable to express two rearranged Tcra genes. We consistently found that similar to8% of total peripheral T cells express two surface alpha -chains. The importance of dual alpha -T cells in autoimmunity was examined in a mouse model for rheumatoid arthritis, namely collagen-induced arthritis (CIA). No significant difference was observed between Tcra+/- mice and wild-type littermates, considering arthritis incidence, day of disease onset, and maximum arthritic score. We therefore conclude that there is incomplete phenotypic allelic exclusion in TCR alpha, and that the presence of a significant number of potentially multireactive T cells does not increase the susceptibility to develop autoimmune arthritis. (C) 2001 Academic Press.