We have previously suggested that the specificities of the entire human MHC-I system should be solved ("the human RB and AP values are defined as described in Table 1 MHC", Buus 1999; Lauemoller et al. 2000) . However, due to the extreme polymorphism of the MHCs, any attempt to address the specificity of the entire MHC system is a significant experimental undertaking. During the past decade, we have established a series of technologies to support a general solution of human MHC class I and II specificities. For MHC-I, this includes (1) a highly efficient E. coli expression system for production of recombinant human and mouse MHC-I molecules (both heavy chain and light chain (β 2 m) molecules) Ostergaard et al. 2001) , (2) a purification system for obtaining the highly active pre-oxidized MHC-I heavy chain species (Ferre et al. 2003) , (3) a high-throughput homogenous peptide-MHC-I binding assay for obtaining large data sets on peptide-MHC-I interactions (Harndahl et al. 2009 ), (4) a positional scanning combinatorial peptide library approach for a robust and unbiased analysis of the specificity of any MHC-I molecule (Stryhn et al. 1996) , (5) an immunobioinformatics approach to generate predictors of the peptide-MHC-I interaction, NetMHCpan, that allows predictions to be made for any human MHC-I molecules, HLA-I, even those that have not yet been covered by existing data set (Hoof et al. 2009; Nielsen et al. 2007) , and finally (6) we have demonstrated that pre-oxidized MHC-I molecules can be used to generate MHC-I tetramers in a simple "one-pot, mix-and-read" manner (Leisner et al. 2008) . Here, we propose that the next goal should be to extend the overall approach to MHC-I molecules of other species of interest. Mouse and rats have been extensively studied in the past, but much less reagents and information have accrued for the MHC-I molecules of other species. Here, we have used an important livestock animal, the pig, as a model system and demonstrated that it indeed is possible to transfer the original human approach to other species. Before attempting to generate a recombinant version of the entire porcine SLA-1*0401 molecule, we grafted the more conserved membrane-proximal "stalk" (the immunoglobulin-like class I heavy chain α 3 and β 2 m domains) of porcine SLA-1*0401 onto the peptide-binding domain of HLA-A*11:01 generating a chimeric human/ porcine MHC-I molecule. This chimeric molecule retained the peptide-binding specificity of the HLA-A*11:01 molecule, and it clearly demonstrated that the recombinant porcine stalk was functional and, by inference, also properly folded. It also suggests that the peptide-binding specificity of the distal domains do not crucially depend upon the identity of the proximal stalk. Further, comparing the ability of human and porcine β 2 m to support MHC-I complex formation using either a human or a porcine MHC-I stalk, we demonstrated that every combination (porcine β 2 m/human-α 3 , porcine β 2 m/porcine-α 3 , human β 2 m/human-α 3 , and human β 2 m/porcine-α 3 ) showed al- most the same heavy chain dose titration with identical half-saturations. These results illustrate the ability for porcine and human β 2 m to support complex formation of SLA molecules and vice versa and suggest evolutionary that the stalk is quite conserved. Next, we generated the entire SLA-1*0401 heavy chain and succeeded in generating complexes using human β 2 m as the light chain and PCSPL as peptide donors. The latter solved the a priori problem of not knowing which peptides would be needed to support proper folding of SLA-1*0401, and it did so in an unbiased manner. Furthermore, this approach is highly efficient since it readily establishes a complete matrix representing the amino acid preference for each amino acid and each position of a nonamer peptide. The specificity of SLA-1*0401 shows two primary anchors: one in positions 9 with a preference for aromatic amino acids and another in position 3 with a preference for negatively charged amino acids. In addition, the SLA-1*0401 features a secondary anchor in position 2 with hydrophobic or polar amino acid preferences.