Evolution and Diversity of the Human Leukocyte Antigen(HLA)

Markov, Peter V.; Pybus, Oliver G.

doi:10.1093/emph/eou033

Cited by 18 publications

(16 citation statements)

References 7 publications

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“…Human leukocyte antigen alleles increased in diversity in response to infectious diseases, and people with allotypes responsive to certain infectious agents are known to have better survival and are likely to be evolutionarily selected ( 20 , 21 ). Therefore, we analyzed whether the allotype restricting CD8 + T cell reactivity to pp65, the major antigen of CMV, is related to the frequency of its allele (Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

“…The significance of HLA class I polymorphisms is that the differences among various HLA molecules and peptides that they present are of sufficient functional importance to be subject to Darwinian natural selection ( 20 ). Given the frequency-dependent conservation of HLA, populations in which specific HLA allotypes are very common (e.g., HLA-A*23:01 in West Africa) may be identified as hot spots for severe disease, endemic persistence, or pathogen emergence ( 21 , 30 ). Thus, a proper understanding of virus-HLA coevolution is instrumental for making informed treatment and vaccine design decisions for a range of major chronic and acute infections ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance

et al. 2017

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To define whether individual human leukocyte antigen (HLA) class I allotypes are used preferentially in human cytomegalovirus (CMV)-specific cytotoxic T lymphocyte responses, CD8+ T cell responses restricted by up to six HLA class I allotypes in an individual were measured in parallel using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C) present in 50 healthy Korean donors. The CD8+ T cell responses to pp65 in the HLA-C allotypes were lower than responses to those in HLA-A and -B allotypes and there was no difference between the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest magnitude and frequency of immune responses to pp65 at each HLA class I locus. However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did not show any immune responses. Although each individual has up to six different HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes, and 2% showed three allotypes that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of specific allotypes. Our results demonstrate that specific HLA class I allotypes are preferentially used in the CD8+ T cell immune response to pp65 and that a hierarchy among HLA class I allotypes is present in an individual.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance

et al. 2017

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“…Interestingly, vaccine candidates show contradictory results concerning efficacy, depending on the inbred murine model used [178]. We need to have in mind that humans, the target population of the vaccines, are quite a heterogeneous population, with more than 7000 HLA alleles identified so far to which we have to add heterozygosity favored by natural selection [179]. To address this issue, we can start by the vaccine engineering phase that should be more and more rational (using reverse vaccinology approaches [180]) and predict the immunogenicity in different human populations, as a proof of principle that is expected to be validated first pre-clinically and then clinically.…”

Section: From "Mice To Man": the Issue Of Animal Models Correlates Omentioning

confidence: 99%

Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing?

Cecílio¹,

Oliveira²,

Cordeiro-da-Silva³

2018

Leishmaniases as Re-Emerging Diseases

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Responsible for up to 30,000 deaths annually, leishmaniasis is a complex spectrum of diseases endemic in 97 countries around the globe. Disease control relies heavily on the early diagnosis and treatment of the active cases (relevant for anthroponotic disease), although it is widely accepted that a prophylactic vaccine for human leishmaniasis is the way to achieve the successful elimination of human disease (taking in consideration the vast list of non-human reservoirs that enable the perpetuation of parasites all around the globe). The notion that infection leads to strong and long-lasting immunity against leishmaniasis supports vaccination as an achievable goal. However, and in spite of the different candidates tested along the years, till date, we still do not have an approved vaccine for humans. In this chapter, we will explore the last advances made in the field of vaccines against Leishmania without forgetting the historical perspective, essential to the understanding of the road already undergone. We will then discuss the correlates of disease and protection, still neither consensual nor definitive, as well as the issue of pre-clinical to clinical translation. The complete understanding of these issues will be essential for the approval of a successful vaccine for human leishmaniasis.

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“…The set of HLA proteins differ from person to person, and each HLA variant has the ability to bind to different repertoires of peptides; this variation consequently determines the immune system’s ability to react to different pathogens. As each HLA variant is potentially able to act against different sets of pathogens, natural selection is hypothesized to favour heterozygous individuals 8 . Both animal and human studies 9 suggest that mating behaviour favours HLA-diverse or HLA-dissimilar individuals.…”

mentioning

confidence: 99%

“…Indeed, couples more dissimilar in their HLA alleles have been reported to be more fertile 10 . Although the specific signalling mechanisms responsible for HLA-mediated mating behaviour remains unclear, it is known that paternal and maternal haplotypes are not randomly matched genetically 8,9 . In spite of that, this information is not part of the selection criteria when an assisted reproductive therapy patient receives or selects a gamete from an unknown external party, and therefore the matching is random at the genetic level.…”

mentioning

confidence: 99%