Evolution of the Class II Major Histocompatibility Complex Alleles in Higher Primates

Kasahara, Masanori; Klein, Dagmar; Fan, Weimin; Gutknecht, Jutta

doi:10.1111/j.1600-065x.1990.tb00037.x

Cited by 45 publications

(15 citation statements)

References 60 publications

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“…The sequencing strategy is depicted in Figure 1; the sequence of the exons is given in Figure 2, that of the introns in Figure 3. The gorilla pseudogene was found in a cosmid library constructed from the genomic DNA of an animal named Sylvia (Kasahara et al 1990. Southern blot hybridization with exon-specific probes revealed that the gene, like the HLA-DRB2 gene, lacked exon 2 and adjacent intron sequences.…”

Section: Resultsmentioning

confidence: 99%

“…Chromosome walking analysis of one of the gorilla Sylvia haplotypes (Kasahara et al 1990) has revealed the DRB2 pseudogene in this species to be flanked on one side by a gene (Gogo-DRBl*08) closely related to the HLA-DRB1*03 gene and on the other side by a gene (Gogo-DRB3) closely related to the HLA-DRB3*01 gene (Kasahara et al 1990. Similarly, in the chimpanzee Hugo haplotype, the Patr-DRB2 is flanked on one side at least by an HLA-DRBl*O3-related gene [Patr-DRBI*03; see Fan and co-workers (1989) and Brfindle and co-workers (1991)].…”

Section: Pa~r-drb2mentioning

confidence: 99%

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The evolutionary origin of the HLA-DR3 haplotype

et al. 1992

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The human HLA-DR3 haplotype consists of two functional genes (DRB1*03 and DRB3*01) and one pseudogene (DRB2), arranged in the order DRB1...DRB2...DRB3 on the chromosome. To shed light on the origin of the haplotype, we sequenced 1480 nucleotides of the HLA-DRB2 gene and long stretches of two other genes, Gogo-DRB2 from a gorilla, "Sylvia" and Patr-DRB2 from a chimpanzee, "Hugo". All three sequences (HLA-DRB2, Gogo-DRB2, Patr-DRB2) are pseudogenes. The HLA-DRB2 and Gogo-DRB2 pseudogenes lack exon 2 and contain a twenty-nucleotide deletion in exon 3, which destroys the correct translational reading frame and obliterates the highly conserved cysteine residue at position 173. The Patr-DRB2 pseudogene lacks exons 1 and 2; it does not contain the twenty-nucleotide deletion, but does contain a characteristic duplication of that part of exon 6 which codes for the last four amino acid residues of the cytoplasmic region. When the nucleotide sequences of these three genes are compared to those of all other known DRB genes, the HLA-DRB2 is seen as most closely related to Gogo-DRB2, indicating orthologous relationship between the two sequences. The Patr-DRB2 gene is more distantly related to these two DRB2 genes and whether it is orthologous to them is uncertain. The three genes are in turn most closely related to HLA-DRBVI (the pseudogene of the DR2 haplotype) and Patr-DRB6 (another pseudogene of the Hugo haplotype), followed by HLA-DRB4 (the functional but nonpolymorphic gene of the DR4 haplotype). These relationships suggest that these six genes evolved from a common ancestor which existed before the separation of the human, gorilla, and chimpanzee lineages. The DRB2 and DRB6 have apparently been pseudogenes for at least six million years (myr). In the human and the gorilla haplotype, the DRB2 pseudogene is flanked on each side by what appear to be related genes. Apparently, the DR3 haplotype has existed in its present form for more than six myr.

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Section: Resultsmentioning

confidence: 99%

Section: Pa~r-drb2mentioning

confidence: 99%

The evolutionary origin of the HLA-DR3 haplotype

et al. 1992

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“…However, the rhesus macaque, by virtue of the relatively close homology of its class II and, to a lesser extent, class I major histocompatibility complex molecules to those of humans (4,17,33), has been a very useful predictor of immune responses in humans. Most recently, the improvement in IFN-␥ responses seen in two macaque studies on RTS,S in a newer adjuvant formulation (35; P. Mettens et al, submitted) did translate to a partial improvement both in the same kinds of in vitro responses and in improved protection rates in a human challenge trial (K. Kester, unpublished), thus adding credence to the macaque model.…”

Section: Discussionmentioning

confidence: 99%

Priming with an Adenovirus 35-Circumsporozoite Protein (CS) Vaccine followed by RTS,S/AS01B Boosting Significantly Improves Immunogenicity toPlasmodium falciparumCS Compared to That with Either Malaria Vaccine Alone

et al. 2007

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The RTS,S/AS02A protein-based vaccine consistently demonstrates significant protection against infection with Plasmodium falciparum malaria and also against clinical malaria and severe disease in children in areas of endemicity. Here we demonstrate with rhesus macaques that priming with a replication-defective human adenovirus serotype 35 (Ad35) vector encoding circumsporozoite protein (CS) (Ad35.CS), followed by boosting with RTS,S in an improved MPL-and QS21-based adjuvant formulation, AS01B, maintains antibody responses and dramatically increases levels of T cells producing gamma interferon and other Th1 cytokines in response to CS peptides. The increased T-cell responses induced by the combination of Ad35.CS and RTS,S/ AS01B are sustained for at least 6 months postvaccination and may translate to improved and more durable protection against P. falciparum infection in humans.Plasmodium falciparum malaria affects millions of people throughout the world annually, and very young children are particularly vulnerable to anemia, cerebral malaria, and death. An effective P. falciparum malaria vaccine could have a profound impact on the lives of the estimated 2 billion at risk (34). The feasibility of development of an effective subunit vaccine against P. falciparum malaria has been convincingly demonstrated by a protein-based antigen (RTS,S), comprising part of the preerythrocytic circumsporozoite (CS) protein, in the AS02A adjuvant system (RTS,S/AS02A; GlaxoSmithKline Biologicals). The RTS,S antigen incorporates part of the CS central tetrapeptide repeat region and C-terminal flanking region, known to contain both B-and T-cell epitopes, into a chimeric gene expressed in Saccharomyces cerevisiae. This construct was named RTS,S to indicate the presence of the CS repeat region (R), T-cell epitopes (T), and hepatitis B virus surface antigen (S) in a mixture of the RTS fusion protein and the S protein that assembles into virus like particles (14, 16).RTS,S formulated in AS02A, a proprietary adjuvant system containing an oil-in-water emulsion and the immune stimulants MPL and QS21, protects approximately 41% of malarianaïve humans against challenge with Plasmodium falciparum sporozoites (18). RTS,S/AS02A efficacy in a field trial was 35% (95% confidence interval [95% CI], 22 to 47%; P Ͻ 0.0001) for protection against first clinical episodes and 49% (95% CI, 12 to 71%; P ϭ 0.02) for protection against severe malaria during an 18-month period for 1-to 4-year-old African children (1, 2). While the unprecedented protection conferred by RTS,S/ AS02A remains partial, several approaches to increasing the efficacy of the vaccine are being studied (16), including new adjuvant formulations and new vaccination strategies.The immune correlates of RTS,S-induced protection are not well defined. However, protection induced by the RTS,S/ AS02A vaccine has been associated with high anti-CS antibody titers, perhaps via inhibition of binding (7) or paralysis of sporozoites (13), or by their opsonization and destruction by phagocytes (32). ...

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“…1). Orthologs of these genes have been described for chimpanzees, gorillas, and rhesus and cynomolgus macaques (8,10,13,21,35,38,39,48,53), whereas similarity to New World monkeys is based on convergent evolution (4,43). In some cases, the absence of exon 2 similarities did not allow the assignation of a particular nonhuman primate DRB allele to a lineage or a locus, as the obvious human equivalent is lacking.…”

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Impact of Endogenous Intronic Retroviruses on Major Histocompatibility Complex Class II Diversity and Stability

Doxiadis

Groot

Bontrop

2008

J Virol

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The major histocompatibility complex (MHC) represents a multigene family that is known to display allelic and gene copy number variations. Primate species such as humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta) show DRB region configuration polymorphism at the population level, meaning that the number and content of DRB loci may vary per haplotype. Introns of primate DRB alleles differ significantly in length due to insertions of transposable elements as long endogenous retrovirus (ERV) and human ERV (HERV) sequences in the DRB2, DRB6, and DRB7 pseudogenes. Although the integration of intronic HERVs resulted sooner or later in the inactivation of the targeted genes, the fixation of these endogenous retroviral segments over long time spans seems to have provided evolutionary advantage. Intronic HERVs may have integrated in a sense or an antisense manner. On the one hand, antisense-oriented retroelements such as HERV-K14I, observed in intron 2 of the DRB7 genes in humans and chimpanzees, seem to promote stability, as configurations/alleles containing these hits have experienced strong conservative selection during primate evolution. On the other hand, the HERVK3I present in intron 1 of all DRB2 and/or DRB6 alleles tested so far integrated in a sense orientation. The data suggest that multigenic regions in particular may benefit from sense introgressions by HERVs, as these elements seem to promote and maintain the generation of diversity, whereas these types of integrations may be lethal in monogenic systems, since they are known to influence transcript regulation negatively.

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Evolution of the Class II Major Histocompatibility Complex Alleles in Higher Primates

Cited by 45 publications

References 60 publications

The evolutionary origin of the HLA-DR3 haplotype

The evolutionary origin of the HLA-DR3 haplotype

Priming with an Adenovirus 35-Circumsporozoite Protein (CS) Vaccine followed by RTS,S/AS01B Boosting Significantly Improves Immunogenicity toPlasmodium falciparumCS Compared to That with Either Malaria Vaccine Alone

Impact of Endogenous Intronic Retroviruses on Major Histocompatibility Complex Class II Diversity and Stability

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