The assembly of functional beta2-microglobulin-free MHC class I molecules that interact with peptides and CD8+ T lymphocytes

Functional MHC class I molecules are expressed on the cell surface in the absence ofβ2‐microglobulin (β2m) light chain that can interact with CD8+ T lymphocytes. Whether their assembly requires peptide binding and whether their recognition by CD8+ T lymphocytes involves the presentation of peptide epitopes remains unknown. We show that β2m‐free H‐2Db assembles with short peptides that are ∼9 amino acid residues in length, akin to ligands associated with completely assembled β2m+ H‐2Db. Remarkably, a subset of the peptides associated with the β2m‐free H‐2Db has an altered anchor motif. However, they also include peptides that contain a β2m+H‐2Db binding anchor motif. Further, the H‐2Kb‐ and H‐2Db‐restricted peptide epitopes derived from SV‐40 T antigen also assemble with H‐2b class I in β2m‐deficient cells and are recognized by epitope‐specific CD8+ T lymphocytes. Taken together our data reveal that functional MHC class I molecules assemble in the absence of β2m with peptides and form CD8+ T lymphocyte epitopes.