You could do something like this:
grd.DataSource = getDataSource();
if (grd.ColumnCount > 1)
{
for (int i = 0; i < grd.ColumnCount-1; i++)
grd.Columns[i].AutoSizeMode = DataGridViewAutoSizeColumnMode.AllCells;
grd.Columns[grd.ColumnCount-1].AutoSizeMode = DataGridViewAutoSizeColumnMode.Fill;
}
if (grd.ColumnCount==1)
grd.Columns[0].AutoSizeMode = DataGridViewAutoSizeColumnMode.Fill;
All columns will adapt to the content except the last one will fill the grid.