Empty MHC class I molecules are known to exist, but they are difficult to investigate. I will explain what we have learnt – using a novel antibody micropatterning two-hybrid assay – about the ability of free heavy chains to form in cis clusters on the cell surface. In the second part, I will focus on our recent development of stable recombinant class I molecules . They can be used to make empty tetramers that load within seconds with any added peptide, with interesting applications in tumor epitope screening.