Assuntos
Concussão Encefálica/fisiopatologia , Transtornos Cognitivos/etiologia , Progressão da Doença , Acelerometria , Adolescente , Concussão Encefálica/psicologia , Criança , Transtornos Cognitivos/fisiopatologia , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Monitorização Ambulatorial , Gravidade do Paciente , Descanso/fisiologiaRESUMO
Specific interactions between killer cell Ig-like receptors (KIRs) and MHC class I ligands have not been described in rhesus macaques despite their importance in biomedical research. Using KIR-Fc fusion proteins, we detected specific interactions for three inhibitory KIRs (3DLW03, 3DL05, 3DL11) and one activating KIR (3DS05). As ligands we identified Macaca mulatta MHC (Mamu)-A1- and Mamu-A3-encoded allotypes, among them Mamu-A1*001:01, which is well known for association with slow progression to AIDS in the rhesus macaque experimental SIV infection model. Interactions with Mamu-B or Mamu-I molecules were not found. KIR3DLW03 and KIR3DL05 differ in their binding sites to their shared ligand Mamu-A1*001:01, with 3DLW03 depending on presence of the α1 domain, whereas 3DL05 depends on both the α1 and α2 domains. Fine-mapping studies revealed that binding of KIR3DLW03 is influenced by presence of the complete Bw4 epitope (positions 77, 80-83), whereas that of KIR3DL05 is mainly influenced by amino acid position 77 of Bw4 and positions 80-83 of Bw6. Our findings allowed the successful prediction of a further ligand of KIR3DL05, Mamu-A1*002:01. These functional differences of rhesus macaque KIR3DL molecules are in line with the known genetic diversification of lineage II KIRs in macaques.
Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Mapeamento de Interação de Proteínas , Receptores KIR3DL1/fisiologia , Receptores KIR3DS1/fisiologia , Animais , Epitopos de Linfócito T/metabolismo , Células HEK293 , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Células K562 , Ligantes , Macaca mulatta , Receptores KIR3DL1/genética , Receptores KIR3DL1/metabolismo , Receptores KIR3DS1/genética , Receptores KIR3DS1/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/metabolismoRESUMO
We here report the genomic organisation of the grey mouse lemur (Microcebus murinus) MHC class II DQ and DR region based on BAC clone analysis. The sequenced Mimu-MHC haplotype spans 343 kb and encompasses the genes TAP2, DOB, DQB, DQA, DRB, DRA, BTNL2 and a further BTNL gene. The DQ and DR genes of this haplotype are not duplicated. Mimu-DOB is not transcribed and represents a pseudogene due to deletions and premature stop codons. Analysis of BAC clone DNA, a cDNA sample and eight genomic DNA samples suggests that Mimu-DRB, Mimu-DQA and Mimu-DQB are highly polymorphic with the majority of peptide-binding residues being affected by polymorphisms. In contrast, Mimu-DRA is moderately polymorphic, and the variable amino acid positions are not part of the peptide-binding region. Phylogenetic analysis of Mimu-DQA and Mimu-DQB and other primate DQA and DQB genes indicates that duplication of DQA and DQB loci occurred in Anthropoidea after the split from Strepsirrhini.
