The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands

HLA-B∗46:01 was formed by an intergenic mini-conversion, between HLA-B∗15:01 and HLA-C∗01:02, in Southeast Asia during the last 50,000 years, and it has since become the most common HLA-B allele in the region. A functional effect of the mini-conversion was introduction of the C1 epitope into HLA-B∗46:01, making it an exceptional HLA-B allotype that is recognized by the C1-specific natural killer (NK) cell receptor KIR2DL3. High-resolution mass spectrometry showed that HLA-B∗46:01 has a low-diversity peptidome that is distinct from those of its parents. A minority (21%) of HLA-B∗46:01 peptides, with common C-terminal characteristics, form ligands for KIR2DL3. The HLA-B∗46:01 peptidome is predicted to be enriched for peptide antigens derived from Mycobacterium leprae. Overall, the results indicate that the distinctive peptidome and functions of HLA-B∗46:01 provide carriers with resistance to leprosy, which drove its rapid rise in frequency in Southeast Asia. Fil: Hilton, Hugo G.. University of Stanford; Estados Unidos Fil: McMurtrey, Curtis P.. Oklahoma State University; Estados Unidos Fil: Han, Alex S.. University of Stanford; Estados Unidos Fil: Djaoud, Zakia. University of Stanford; Estados Unidos Fil: Guethlein, Lisbeth A.. University of Stanford; Estados Unidos Fil: Blokhuis, Jeroen H.. University of Stanford; Estados Unidos Fil: Pugh, Jason L.. University of Stanford; Estados Unidos Fil: Goyos, Ana. University of Stanford; Estados Unidos Fil: Horowitz, Amir. University of Stanford; Estados Unidos Fil: Buchli, Rico. Pure Protein LLC; Estados Unidos Fil: Jackson, Ken W.. Oklahoma State University; Estados Unidos Fil: Bardet, Wilfred. Oklahoma State University; Estados Unidos Fil: Bushnell, David A.. University of Stanford; Estados Unidos Fil: Robinson, Philip J.. University of Stanford; Estados Unidos Fil: Mendoza, Juan L. University of Stanford; Estados Unidos Fil: Birnbaum, Michael E.. University of Stanford; Estados Unidos Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Garcia, K. Christopher. University of Stanford; Estados Unidos Fil: Hildebrand, William H.. Oklahoma State University; Estados Unidos Fil: Parham, Peter. University of Stanford; Estados Unidos