A normal antibody response to T cell-dependent Ag requires physical co
ntact between Ag-specific B and T cells. Because such Ag-specific cell
s are rare in vivo, we sought to identify an in vivo site where they p
hysically contact each other. We examined the Ag specificity of T cell
s in germinal centers (GC) in lymph nodes, where it is known that Ag-s
pecific B cells proliferate and mature. We investigated the Ag specifi
city of GC T cells in situ by examining two characteristics: 1) expres
sion of certain V(alpha) and V(beta) TCR families; and 2) incorporatio
n of bromodeoxyuridine into T cell DNA after exposure to Ag as an inde
x of Ag-induced proliferation. When GC were induced in mice with cytoc
hrome c and myelin basic protein, the GC T cells were found to prefere
ntially express V(alpha)11 and V(beta)8 TCR families, which are, respe
ctively, the dominant TCR families in these two responses. Furthermore
, GC T cells have proliferated upon exposure to the Ag that induced GC
formation. Taken together, these results demonstrate that GC must rec
ruit and retain Ag-specific T cells, thus implicating the GC as an in
vivo site where Ag-specific T and B cells interact.