RESUMO
The mouse CD1 system is formed by two closely related genes named Cd1d1 and Cd1d2. Cd1d1 encodes a molecule that presents antigens to NKT cells. The function of the Cd1d2 gene has not been elucidated. Here we described a method to analyse variations in mouse Cd1 genes. We found a new allele for Cd1d2 characterized by a point mutation, resulting in a replacement of alanine at position 176 by a valine.
Assuntos
Antígenos CD1/genética , Alanina/química , Alelos , Sequência de Aminoácidos , Animais , Antígenos CD1d , Sequência de Bases , Variação Genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Dados de Sequência Molecular , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Valina/químicaRESUMO
We characterized the MHC-related 1 ( MR1) locus in two nonhuman primates species, Pongo pygmaeus and Pan troglodytes. MR1 cDNA sequences encoding several isoforms generated through alternative splicing were observed in both species. Amino acid alignment between the five species in which MR1 has been characterized to date - human, chimpanzee, orangutan, mouse, and rat - reveals a very high degree of conservation specially in the alpha1 and alpha2 domains of the molecule. The main differences concentrate in the transmembrane and cytoplasmic domains. In the three primates species there is a lysine residue inside the putative transmembrane domain which is not present in rodents. Furthermore, the MR1 cytoplasmic region is longer in rodents, with a conserved serine-containing motif that could be involved in endocytosis; remarkably, this motif is absent in the three primate species. We also describe the presence in the chimpanzee of a sequence homologous to the MR1P1 pseudogene previously found in humans.
Assuntos
Genes MHC Classe I/genética , Antígenos de Histocompatibilidade Classe I/genética , Pan troglodytes/genética , Pongo pygmaeus/genética , Sequência de Aminoácidos , Animais , Linhagem Celular Transformada , Clonagem Molecular , Sequência Conservada , Humanos , Antígenos de Histocompatibilidade Menor , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Homologia de Sequência de AminoácidosRESUMO
CD1 is a family of proteins structurally related to major histocompatibility complex (MHC) molecules and specialized in presenting lipids or glycolipids to T cells. In humans, there are five CD1 genes (CD1A to CD1E). It has been shown that, in contrast with classical MHC genes, CD1 loci display a very limited polymorphism. In the present work we describe two novel CD1E alleles found in two healthy Caucasian individuals. One allele differs from the wild-type by a point mutation resulting in a replacement of arginine at position 154 by a tryptophan. In the second allele we found a substitution of the leucine 184 by a proline.
Assuntos
Alelos , Antígenos CD1/química , Antígenos CD1/genética , Sequência de Aminoácidos , Antígenos CD1/imunologia , Sequência de Bases , Éxons , Humanos , Dados de Sequência Molecular , Mutação Puntual/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , Polimorfismo Conformacional de Fita Simples , Estrutura Terciária de ProteínaRESUMO
Human MR1 is a recently discovered, ubiquitously transcribed gene very similar to the HLA class I loci and of unknown function. Mouse and rat MR1 sequences have also been described showing high similarity with the human gene. The goal of this work was to investigate if human MR1 was polymorphic. We have found that DNA sequences of MR1-specific polymerase chain reaction (PCR) products obtained from samples of diverse ethnic origin were invariant except in one case in which two silent mutations were detected. We also found an MR1-like sequence displaying significant differences with the previously described, the most remarkable of which is a STOP codon in the alpha2 domain indicating that is a pseudogene.
