T cells using the gammadelta T cell receptor (TCR) are abundant in mucosal and epidermal tissues in mice. Most studies of mucosal gammadelta T cells, however. have examined cells from the intestinal mucosa, whereas little is known about the presence or function of gammadelta T cells in the oral cavity. To better understand the involvement of oral gammadelta T cells in immunity, we have characterized TCR variable gamma-gene usage in the buccal epithelium from normal mice, and from mice challenged locally with a non-replicating antigen (bovine serum albumin [BSA]) or by influenza-virus infection as a replicating antigen. Our findings demonstrate a restricted use of Vgamma genes by buccal gammadelta T cells, consisting primarily of Vgamma1.2, Vgamma3, and Vgamma5, with minimal use of Vgamma2 and Vgamma4 genes. Of particular interest, 3-4 days post-antigen challenge with BSA, there was a precipitous drop in the level of expression of Vgamma1.2, Vgamma3, and Vgamma5 genes, and to a lesser extent for the Vgamma2 gene, whereas Vgamma4 gene expression increased between days I and 2 post-priming. In influenza-infected mice, a similar pattern was observed for the Vgamma2 and Vgamma5 genes, but not other Vgamma genes, The immune-modulating effects of oral antigen exposure on buccal gammadelta T cells suggest that these cells are functionally involved in the local immune response to both replicating and non-replicating antigens in oral mucosal surfaces. (C) 2002 Elsevier Science (USA). All rights reserved.