Abstract <p>Swine leukocyte antigen class I (SLA-I) molecules are swine orthologs of human MHC class I molecules and are encoded by three classical loci, <i>SLA-1</i>, <i>SLA-2</i>, and <i>SLA-3</i>. By engaging T-cell receptors (TCRs), these cell-surface proteins present antigenic peptides, whose binding specificity is largely dictated by the architecture of the peptide-binding groove (PBG) and its constituent pockets. Although early SLA-I research primarily emphasized molecular and functional features, recent advances in structural biology have yielded an increasing number of crystal structures of SLA-I–peptide complexes, providing critical insights into the principles of peptide presentation and T-cell recognition in pigs. In this review, we examine the structural features of SLA-I molecules, focusing on the PBG and binding pockets that accommodate peptide anchor residues. Structural studies revealed that the SLA-I PBG, while architecturally conserved, exhibits pronounced allelic polymorphism and plasticity, predominantly within its six binding pockets (A–F). A key insight is the profound functional impact of micropolymorphisms; for instance, single-residue variations in pockets such as D can dramatically alter the peptide-binding specificity and repertoire. Finally, we highlight current knowledge gaps and future research directions to facilitate the exploitation of SLA-I structural features for targeted vaccine design and immunotherapeutic development, thus addressing the challenges of porcine immune recognition.</p> Graphical abstract <p></p>