The formation of a trimeric complex, composed of heavy chain (HC), beta(2)-microglobulin (beta(2)m) and antigenic peptide, is generally believed to be a prerequisite for the expression of HLA class I molecules at the cell surface in vivo. Therefore, a possible role in immunological processes for HC/beta(2)m complexes devoid of peptide has not been seriously considered. Using a novel HLA-B*2705-transgenic rat model and monoclonal antibodies that distinguish between structurally different forms of HLA-B27 molecules, we demonstrate here that class I molecules which appear to lack antigenic peptides are expressed in abundance on a variety of cell types in lymphoid organs. These results imply a role for structurally diverse, possibly empty, MHC molecules in physiological T cell selection which has so far not been sufficiently appreciated.