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Class I HLA haplotypes form two schools that educate NK cells in different ways.

ABSTRACT: Natural killer (NK) cells are lymphocytes having vital functions in innate and adaptive immunity, as well as placental reproduction. Controlling education and functional activity of human NK cells are various receptors that recognize HLA class I on the surface of tissue cells. Epitopes of polymorphic HLA-A,-B and -C are recognized by equally diverse killer cell immunoglobulin-like receptors (KIR). In addition, a peptide cleaved from the leader sequence of HLA-A,-B or -C must bind to HLA-E for it to become a ligand for the conserved CD94:NKG2A receptor. Methionine/threonine dimorphism at position -21 of the leader sequence divides HLA-B allotypes into a majority having -21T that do not supply HLA-E binding peptides and a minority having -21M, that do. Genetic analysis of human populations worldwide shows how haplotypes with -21M HLA-B rarely encode the KIR ligands: Bw4+HLA-B and C2+HLA-C KIR. Thus there are two fundamental forms of HLA haplotype: one preferentially supplying CD94:NKG2A ligands, the other preferentially supplying KIR ligands. -21 HLA-B dimorphism divides the human population into three groups: M/M, M/T and T/T. Mass cytometry and assays of immune function, shows how M/M and M/T individuals have CD94:NKG2A+ NK cells which are better educated, phenotypically more diverse and functionally more potent than those in T/T individuals. Fundamental new insights are given to genetic control of NK cell immunity and the evolution that has limited the number of NK cell receptor ligands encoded by an HLA haplotype. These finding suggest new ways to dissect the numerous clinical associations with HLA class I.

SUBMITTER: Horowitz A

PROVIDER: S-EPMC5110269 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Class I HLA haplotypes form two schools that educate NK cells in different ways.

Horowitz Amir A Djaoud Zakia Z Nemat-Gorgani Neda N Blokhuis Jeroen J Hilton Hugo G HG Béziat Vivien V Malmberg Karl-Johan KJ Norman Paul J PJ Guethlein Lisbeth A LA Parham Peter P

Science immunology 20160909 3

Natural killer (NK) cells are lymphocytes having vital functions in innate and adaptive immunity, as well as placental reproduction. Controlling education and functional activity of human NK cells are various receptors that recognize HLA class I on the surface of tissue cells. Epitopes of polymorphic HLA-A,-B and -C are recognized by equally diverse killer cell immunoglobulin-like receptors (KIR). In addition, a peptide cleaved from the leader sequence of HLA-A,-B or -C must bind to HLA-E for it ...[more]

PMID: 27868107

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Project description:Here we studied HLA blocks and haplotypes in a group of 218 Lacandon Maya Native American using a high-resolution next generation sequencing (NGS) method. We assessed the genetic diversity of HLA class I and class II in this population, and determined the most probable ancestry of Lacandon Maya HLA class I and class II haplotypes. Importantly, this Native American group showed a high degree of both HLA homozygosity and linkage disequilibrium across the HLA region and also lower class II HLA allelic diversity than most previously reported populations (including other Native American groups). Distinctive alleles present in the Lacandon population include HLA-A*24:14 and HLA-B*40:08. Furthermore, in Lacandons we observed a high frequency of haplotypes containing the allele HLA-DRB1*04:11, a relatively frequent allele in comparison with other neighboring indigenous groups. The specific demographic history of the Lacandon population including inbreeding, as well as pathogen selection, may have elevated the frequencies of a small number of HLA class II alleles and DNA blocks. To assess the possible role of different selective pressures in determining Native American HLA diversity, we evaluated the relationship between genetic diversity at HLA-A, HLA-B and HLA-DRB1 and pathogen richness for a global dataset and for Native American populations alone. In keeping with previous studies of such relationships we included distance from Africa as a covariate. After correction for multiple comparisons we did not find any significant relationship between pathogen diversity and HLA genetic diversity (as measured by polymorphism information content) in either our global dataset or the Native American subset of the dataset. We found the expected negative relationship between genetic diversity and distance from Africa in the global dataset, but no relationship between HLA genetic diversity and distance from Africa when Native American populations were considered alone.

Project description:BackgroundDurations of exclusive breastfeeding (EBF) and predominant breastfeeding (PBF) from two different assessments, among the same mother-infant population, were investigated to determine the degree to which the assessments yielded overlapping results.MethodsThirty Ugandan mother-infant pairs were followed up weekly from birth to three months of age with weekly short-time feeding recall: the 24-hour recall asked prior to the 1-week recall. In addition, at week 6 and 12 dietary recalls since-birth were conducted. Variables for the duration of EBF and PBF were created from the short-time feeding recalls and the dietary recalls since-birth, respectively. Mean durations of EBF and PBF from the two assessments were compared with Kaplan Meier analysis at week 6 and 12. Reproducibility of dietary recall instruments was also assessed.ResultsAt six weeks postpartum the mean durations of EBF were 0.50 weeks (95% CI: 0, 1.02) according to the weekly short-time recalls and 1.51 weeks (95% CI: 0.66, 2.35) according to the recall since-birth (Mantel-Cox test, p = 0.049). The mean durations of PBF were 4.07 weeks (95% CI: 3.38, 4.77) according to the frequent short-time recalls and 4.50 weeks (95% CI: 3.93, 5.07) according to the recall since-birth, (Mantel-Cox-test, p = 0.82). At twelve weeks the mean durations of EBF were 0.5 weeks (95% CI: 0, 1.1) according to the weekly short-time recalls and 1.4 weeks (95% CI: 0.1, 2.7) according to the recall since-birth (Mantel-Cox-test, p = 0.15). The mean durations of PBF were 5.2 weeks (95% CI: 3.9, 6.5) according to the weekly short-time recalls and 6.6 weeks (95% CI: 5.4, 7.8) according to recall since-birth (Mantel-Cox-test, p = 0.20). Reports of feeding categories and early feeding practices showed high reproducibility.ConclusionComparing duration of EBF and PBF in this group of mother-infant pairs showed overlapping results from the weekly short-time assessment and the recall since-birth at twelve weeks, with the latter yielding slightly longer duration of the respective feeding modalities. The retrospective recall since-birth could be assessed as a cost-reducing tool compared to the frequent follow-up addressing duration of respective infant feeding modalities for evaluation of programmes promoting safer infant feeding practices.Trial registrationThe study was part of formative studies for the ongoing study PROMISE EBF registered at http://clinicaltrials.gov, NCT00397150.

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Class I HLA haplotypes form two schools that educate NK cells in different ways.

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Class I HLA haplotypes form two schools that educate NK cells in different ways.

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