Structural basis of cross-allele presentation by HLA-A*0301 and HLA-A*1101 revealed by two HIV-derived peptide complexes.

Human leukocyte antigens (HLA) are initially classified by serotyping but recently can be re-grouped by their peptide-presentation characteristics into supertypes. Both HLA-A0301 and HLA-A1101 are grouped into A3 supertype. Although a number of cross-presented T cell epitopes of HLA-A0301 and HLA-A1101 have been identified, the molecular mechanisms of cross-presentation remain elusive. Herein, the structures of HLA-A0301 with two HIV-derived immunodominant T cell epitopes were solved and their characteristics in comparison with HLA-A1101 presenting the same peptides were analyzed. The comparable structures of HLA-A0301 and HLA-A1101 with subtle differences illustrate the common modes of cross-presented peptides and the strict HLA-restriction of T cell receptor (TCR)-recognition.