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J Martinez-Laso

Publications and source records attributed to J Martinez-Laso.

At least 19 recordsLinked to original sources
PubMed1999

Evolution of MHC-G in primates: a different kind of molecule for each group of species.

When MHC-G molecules in primates (New World and Old World monkeys, Anthropoids and humans) were compared phylogenetically, very different evolutionary patterns within each species were found; their molecules did not have a straight forward and linear development throughout the postulated evolutionary pathway of primates. The earlier New World monkeys (South America) had relatively more alleles and the polymorphism was placed in the T-cell receptor (TcR), NK receptors and antigen binding sites; MHC-G probably works as a classical class I presenting molecule in these monkeys. MHC-G intron 2 from New World monkeys does not show the typical 23 bp deletion found in all other more recent primate species. Thus, it is possible that MHC-G molecules in New World monkeys belong to a different lineage than the MHC from higher primates. Another early lineage, Eurasian Old World monkeys, shows stop codons at exon 3: MHC-G proteins lacking the alpha2 domain may functionally suffice or otherwise reading-through stop-codon translational mechanisms may exist, as shown for other genes. Orangutans show lower (but significant) polymorphism than New World monkeys at NK, TcR and antigen binding regions; gorilla and chimpanzee show very low polymorphism. Humans only show three different HLA-G proteins with changes not affecting NK, TcR or antigen binding sites. It is observed that the more exposed the mother to allogeneic fetuses (polygamy), the less polymorphic HLA-G is observed within a given species. The data are concordant with the postulated immune inhibitory function for MHC-G in Old World monkeys, anthropoids and humans both at placental and inflammatory level.

Amino Acid Sequence↗
PubMed1999

Evolutionary relationships between HLA-B alleles as indicated by an analysis of intron sequences.

The HLA-B locus is the most polymorphic of the class I genes encoded within the human major histocompatibility complex. This polymorphism is mainly located in exons 2 and 3, which code for the molecule's alpha1 and alpha2 domains and includes the antigenic peptide binding site. However, information about adjacent non-coding regions (introns 1 and 2) has not been extensively reported but could be very important in establishing an understanding of the evolutionary mechanisms involved in the polymorphism generation of HLA-B and the Mhc loci. In the present work, introns 1 and 2 of 14 HLA-B alleles are studied and their significance is discussed; 10 have been sequenced in our own laboratory and the other 4 have been previously reported by others. Different serological families share the complete intron 1 sequence; at this region, 12 out of 14 HLA-B alleles could be included in four groups with the same intron 1 sequence: a) B*0702, B*4201, B*4801; b) B*27052, B*4002, B*4011; c) B*40012, B*4101, including B*4501, B*5001 (these latter two alleles have specific characteristics in both introns 1 and 2, which may reflect a common evolutionary pathway); and d) B*44031, B*44032. The other alleles, B*1402, and B*1801, do not have identical intron 1 sequences compared to any of the described groups, but share many similarities with them. The B*1801 evolutionary pathway seems to be very specific since it branches separately from other alleles both in intron 1 and intron 2 dendrograms. On the other hand, HLA-B allelic group distribution and similarities according to intron 1 sequences were not confirmed when using intron 2, especially in the cases of B*4002, B*4101 and B*4801. This would suggest that both point mutations fixed by genetic drift and gene conversion events are involved in HLA-B diversification. The latter events could be supported by the strong homology between intron 1 and, to a lesser extent, intron 2, and also the CG content within them. Finally, the precise knowledge of these non-coding regions could be important for developing DNA base typing strategies for the HLA-B alleles.

Alleles↗
PubMed1999

HLA in the Azores Archipelago: possible presence of Mongoloid genes.

The HLA profile of the Azoreans has been compared with those of other world populations in order to provide additional information regarding the history of their origins. The allele frequencies, genetic distances between populations, correspondence analyses and most frequent haplotypes were calculated. Our results indicate that the Azorean population most likely contains an admixture of high-frequency Caucasoid, Mongoloid and, to a lesser degree, Negroid HLA genes. The middle Atlantic Azores Archipelago was officially colonized by the Portuguese after 1439 and historical records are concordant with the existence of Caucasoid and Negroid population. However, Mongoloid genes were not suspected, but the Oriental HLA haplotypes A24-B44-DR6-DQ1, A29-B21-DR7-DQ2 and A2-B50-DR7-DQ2 are the fourth, fifth and sixth most frequent ones in Azores. A correspondence analysis shows that the Azorean population is equidistant from Asian and European populations and genetic distances are in some cases closer to the Asian than to European ethnic groups, and never are significantly different; also, B*2707 subtype is found in Asians and Azoreans (but not in Europeans) and the same Machado-Joseph Disease founder haplotypes (Chr 14) are found in both Japanese and Azoreans. It is proposed that a Mongoloid population exists in Azores; whether, the arrival occurred prior to discovery is undetermined.

Alleles↗
PubMed1998

Allelic diversity at the primate MHC-DMB locus: presence of a conserved tyrosine inhibitory motif in the cytoplasmic tail.

Ten new primate Mhc-DMB complete cDNA sequences have been obtained in chimpanzee (n=four), gorilla (n=three) and orangutan (n=three); this gene has not been previously studied in these species. Exonic allelism has been recorded all along the molecule domains and also in the leader peptide, but not in the transmembrane segment. An analysis of the residues critical in the conformation of the Mhc-DR peptide-binding site was done in order to look for a Mhc-DR homologue site; synonymous substitutions are favoured in this homologous HLA-DM region. This is another finding that supports the possibility that DM could not be typically presenting molecules. The immunoreceptor inhibition motif Tyr 230-Thr/Ser 231-Pro 232-Leu 233 (ITIM) is invariantly present in apes for at least 15 million years, and may have a double function: 1) To direct DMB-DMA molecules from the endoplasmic reticulum or cell surface towards the endosomal/lysosomal class II compartment and 2) to send an inhibitory signal to the cell in order to stop synthesis of unnecessary HLA-DR molecules, once all available antigenic peptides are loaded. Other molecules, like NK-cell receptors and Fc receptors, bear this type of tyrosine-based inhibitory motifs in order to switch off specific cell functions. DMB molecules (as previously shown in C4d molecules) do not present species-specific motifs in common chimpanzee, suggesting that this species is very close to gorilla or man; also, DMB, like C4d molecules, do not show a trans-species evolution pattern, suggesting the existence of extensive homogenization of DMB genes within each species or a recent generation of alleles. Finally, a clade grouping human and gorilla DMB cDNA sequences is obtained using a dendrogram (as for C4d trees); this is in contrast to others' results that obtain a human/chimpanzee clade using different DNA sequences.

Alleles↗
PubMed1997

Description of a new HLA-E (E*01031) allele and its frequency in the Spanish population.

An HLA-E polymorphism study by oligotyping and DNA sequencing was carried out in the Spanish population. As a result, a new HLA-E allele (E*01031) initially assigned by polymerase chain reaction oligotyping as E*0104 was found. This allele presents a synonymous change at codon 77 (AAT-->AAC; Asn) when compared with the E*01032 allele. This position is located in the alpha-helix (alpha 1-domain) and is involved in the peptide binding region of the hypothetical HLA-E molecule. Among 60 Spanish individuals, HLA-E*0101 presents the highest phenotype frequency, followed in decreasing order by E*01032, E*01031 (new allele), and E*0102. Also, new partial intron 1 and complete intron 2 sequences from E*0101, E*01031, and E*01032 are described; the sequences are identical among the three forms. However, the intron 2 sequence of the E*0102 allele bears a two-base deletion not found in apes.

Alleles↗
PubMed1997

Generation of the HLA-B35, -B5, -B16, and B15 groups of alleles studied by intron 1 and 2 sequence analysis.

HLA-B is the most polymorphic of the major histocompatibility complex classical class I loci. This polymorphism is mainly in exons 2 and 3, which code for the molecule's alpha 1 and alpha 2 domains and include the antigenic peptide binding site. Recent studies have indicated that not only exons but also the intron 2 region may be involved in the generation of certain HLA-B alleles such as B*3906 and B*1522. To study the degree of intron 2 participation and the mechanisms that generate polymorphism at the HLA-B locus, intron 1 and 2 sequences from the HLA-B35, -B5, -B16 and -B15 groups of alleles were obtained. A group-specific intronic polymorphism was found: namely, B*5301 shows intron 1 and 2 sequences identical to those found in all B35 alleles studied. On the other hand, B*5101 and B*52012 show the same intron 1 and 2 sequences and their intron 1 is the same as that found in the B35 group. This suggests that B5 and B35 groups of alleles may have arisen from a common ancestor. All known B16 alleles show the same introns 1 and 2, with the exception of B*39061 and B*39062, and all B15 alleles also bear the same introns 1 and 2, with the exception of B*1522. Variability at intron 1 is more restricted than at intron 2, and the use of intron 1 for HLA-B allele phylogenetic analysis is better for grouping alleles of a postulated common origin. In conclusion, there is a remarkable conservation of intronic sequences within related HLA-B alleles, which probably reflects a common origin and perhaps a selective force avoiding DNA changes. Intronic sequences are also potentially useful to design DNA typing strategies.

Alleles↗
PubMed1997

Complete nucleotide sequence of the HLA-DRB1 *1302 allele.

Sequencing studies of HLA class II molecules have focused almost exclusively on its exon 2. The complete cDNA sequence of the DRB*1302 allele is reported here for the first time. A conservative polymorphism was detected outside the exon 2 at residue 206; these changes can only be recorded if complete cDNA sequences are studied, and may be of value in drawing evolutive inferences.

Base Sequence↗
PubMed1997

High polymorphism of Mhc-E locus in non-human primates: alleles with identical exon 2 and 3 are found in two different species.

Thirteen Mhc-E new sequences were found in eight individuals belonging to the Cercopithecinae family, i.e.: Macaca mulatta, Macaca fascicularis and Cercopithecus aethiops when studying E locus polymorphism. No changes were found in the invariant residues which are required for the correct conformation of the peptide presenting region which are conserved in classical Mhc class I molecules from fish and reptiles to humans; however, polymorphism of Mhc-E alleles is not limited to the three typical hypervariable regions per domain as it is in classical class I alleles. The rate of synonymous and nonsynonymous substitutions in the DNA sequence corresponding to the antigen binding site, compared to the remainder of exons 2 and 3 shows that the peptide-binding site is under high evolutionary pressure for stability since only synonymous substitutions have been found to be accepted in apes. Also, a clear example of trans-species evolution of allelism is found: two identical exon 2 and exon 3 sequences there exist belonging to individuals from different species (Mamu-Mhc-E*0101 and Mafa-Mhc-E*04). In addition, two Macaca mulatta individuals show an Mhc-E locus duplication. Finally, phylogenetic tree analysis shows that Mhc class I molecules found in Saguinus oedipus (described as Mhc-G homologues) are closer to Mhc-E sequences.

Alleles↗
PubMed1996

Description of a novel HLA-B35 (B*3514) allele found in a Mexican family of Nahua Aztec descent.

A new allele, HLA-B*3514, has been found in a Mexican family from Nahua descent. Its exon 2 is identical to that of B*3501 allele, but exon 3 bears a 3-base difference at codons 152 and 156, which results in Val-->Glu and Leu-->Trp changes, respectively, in the corresponding HLA molecule at the peptide-binding site. These substitutions may have originated from a DNA stretch donation from an allele belonging to the B15 group, enabling HLA-B*3514 to cope with the presentation of a new set of antigenic peptides. The high frequency of serologic B35 in Amerindians, together with the variety of B35 alleles detected by DNA sequencing in these populations, suggest that a frequent B35 subtype was present in the founder population and that several B35 subtypes may have been recently generated, probably due to the abrupt arrival of new pathogens following European invasions.

Alleles↗