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View Full Version : 'immune gene' in Neanderthals



Jean M
12-02-2013, 10:48 PM
Sebastian Temme et al., A novel family of human lymphocyte antigen class II receptors may have its origin in archaic human species, Journal of Biological Chemistry, online November 8, 2013
http://dx.doi.org/10.1074/jbc.M113.515767


HLA class II α and β chains form receptors for antigen presentation to CD4+ T cells. Numerous pairings of class II α and β subunits from the wide range of haplotypes and isotypes may form, but most of these combinations, in particular those produced by isotype mixing, yielded mismatched dimers. It is unclear how selection of functional receptors is achieved. At the atomic level, it is not known which interactions of class II residues regulate selection of matched αβ heterodimers and the evolutionary origin of matched isotype mixed dimer formation. In this study, we investigated assembly of isotype-mixed HLA class II α and βheterodimers. Assembly and carbohydrate maturation of various HLA-class II isotype-mixed α and β subunits was dependent on the groove-binding section of the invariant chain (Ii). By mutation of polymorphic DPβ sequences, we identified two motifs, K69 and GGPM84-87, which are engaged in Ii-dependent assembly of DPβ with DRα. We identified five members of a family of DPβ chains containing K69 and GGPM 84-87, which assemble with DRα. The K/GGPM motif is present in the DPβ sequence of the Neandertal genome and this ancient sequence is related to the human allele DPB1*0401. By site- directed mutagenesis we inspected Neandertal amino acid residues which differ from the DPB1*0401 allele and whether matched heterodimers are formed by assembly of DPβ mutants with DRα. Since the *0401 allele is rare in the Sub-Saharan population but frequent in the European population it may have arisen in modern humans by admixture with Neandertals in Europe.

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