Common and well‐documented <scp>HLA</scp> alleles: 2012 update to the <scp>CWD</scp> catalogue

Mack, Steven J.; Cano, Pedro; Hollenbach, Jill A.; He, Jun; Hurley, Carolyn Katovich; Middleton, Derek; Moraes, M. E.; Pereira, Shalini; Kempenich, Jane; Reed, Elaine F.; Setterholm, Michelle; Smith, Anajane G.; Tilanus, Marcel G.J.; Torres, Margareth; Varney, Michael D.; Voorter, C. E. M.; Fischer, Gottfried; Fleischhauer, Katharina; Goodridge, Damian; Klitz, William; Little, Ann‐Margaret; Maiers, Martin; Marsh, Steven G.E.; Müller, Carlheinz; Noreen, Harriet; Rozemuller, Erik H.; Sanchez‐Mazas, Alicia; Senitzer, David; Trachtenberg, Elizabeth; Fernández-Viña, Marcelo

doi:10.1111/tan.12093

Cited by 207 publications

(232 citation statements)

References 78 publications

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“…Respective four-digit types were assigned using the catalogue of common and well-documented (CWD) human leukocyte antigen alleles (46,(48)(49)(50)(51). The plausibility of four-digit HLA-DR and HLA-DQ types was further corroborated against the allele frequency net database, an online resource containing information on the frequencies of immune genes, their corresponding alleles and haplotypes in different populations (52).…”

Section: Study Population and Case Ascertainmentmentioning

confidence: 99%

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

Sapir‐Pichhadze

Tinckam

Quach

et al. 2015

American Journal of Transplantation

116

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We conducted a nested case-control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA-DR and -DQ incompatibility at the eplet level. Cases (n ¼ 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n ¼ 104) with a similar follow-up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios [OR] of 2.84 [95% confidence interval (CI): 1.03, 7.84] and 4.62 [95% CI: 1.51, 14.14]) in the presence of 27-43 and >43 HLA-DR þ DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA-DR þ DQ eplet mismatches. Our study suggests that minimization of HLA-DR þ DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study.

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Section: Study Population and Case Ascertainmentmentioning

confidence: 99%

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

Sapir‐Pichhadze

Tinckam

Quach

et al. 2015

American Journal of Transplantation

116

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“…An allele subset was selected containing: (a) HLA-E (n = 6), HLA-F (n = 3), and HLA-G (n = 17) complete protein sequences sampling allelic variability at each locus; (b) all the "common" HLA-A (n = 66), HLA-B (n = 123), and HLA-C (n = 39) alleles, as defined in the catalog of Common and Well Defined alleles, release 3.9.0, Table S1 in Mack et al [34]. Briefly, alleles are defined as "common" if they are represented at a frequency >0.001 in multiple populations (n = >1.500), or in every region of the world.…”

Section: Computer-assisted Analysismentioning

confidence: 99%

Monoclonal antibodies to HLA‐E bind epitopes carried by unfolded β₂m‐free heavy chains

Tremante¹,

Monaco²,

Ingegnere³

et al. 2015

Eur J Immunol

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Since HLA-E heavy chains accumulate free of their light β 2 -microglobulin (β 2 m) subunit, raising mAbs to folded HLA-E heterodimers has been difficult, and mAb characterization has been controversial. Herein, mAb W6/32 and 5 HLA-E-restricted mAbs (MEM-E/02, MEM-E/07, MEM-E/08, DT9, and 3D12) were tested on denatured, acid-treated, and natively folded (both β 2 m-associated and β 2 m-free) HLA-E molecules. Four distinct conformations were detected, including unusual, partially folded (and yet β 2 m-free) heavy chains reactive with mAb DT9. In contrast with previous studies, epitope mapping and substitution scan on thousands of overlapping peptides printed on microchips revealed that mAbs MEM-E/02, MEM-E/07, and MEM-E/08 bind three distinct α1 and α2 domain epitopes. All three epitopes are linear since they span just 4-6 residues and are "hidden" in folded HLA-E heterodimers. They contain at least one HLA-E-specific residue that cannot be replaced by single substitutions with polymorphic HLA-A, HLA-B, HLA-C, HLA-F, and HLA-G residues. Finally, also the MEM-E/02 and 3D12 epitopes are spatially distinct. In summary, HLA-E-specific residues are dominantly immunogenic, but only when heavy chains are locally unfolded. Consequently, the available mAbs fail to selectively bind conformed HLA-E heterodimers, and HLA-E expression may have been inaccurately assessed in some previous oncology, reproductive immunology, virology, and transplantation studies.Keywords: Conformation r HLA-E r HLA-A r -B r -C r mAbs r β 2 -microglobulin (β 2 m) Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionBeing the ligand of both the conserved CD94/NKG2A immune receptor and the variable TCR, the oligomorphic HLA-E molecule bridges classical and nonclassical HLA class I antigens [1]. Often classified among the latter, HLA-E may rather be considered an inbetweener. This definition also applies to HLA-C, since this is the least polymorphic among classical (HLA-A, -B, -C) Correspondence: Dr. Patrizio Giacomini e-mail: giacomini@ifo.it class I antigens, and shares with HLA-E several unorthodox properties, such as selective peptide binding, poor association with β 2 m [2-4], and massive accumulation in a β 2 m-free form [5,6].Although often unappreciated, unfolded and β 2 m-free heavy chains may share epitopes with fully folded HLA class I heterodimers. These "intermediate" folds may confound the assignment of antibody specificity. For instance, a mAb called Q1/28 binds HLA-B but not HLA-C when heavy chains are β 2 massociated, and HLA-C but not HLA-B when heavy chains are β 2 m-free [7]. Likewise, mAbs MEM-E/07 and MEM-E/08 bind β 2 m-free HLA-E, but cross-react with HLA-A, -B, -C heavy chainswww.eji-journal.eu Eur. J. Immunol. 2015. 45: 2356-2364 Molecular immunology 2357 associated with β 2 m [6]. Therefore, mAbs to inbetweeners require thorough characterization, including their systematic testing on both the β 2 m-associated and the β 2 m-free heavy chains specified by ...

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“…Among all human genes showing some evidence of natural selection, those coding for HLA molecules involved in adaptive immune response [15] exhibit a particularly high level of polymorphism in human populations [16,17] . This observation has been explained by many causes [for a review, see 18 ], the most realistic being perhaps an increased immune protection of heterozygous individuals in pathogenic environments (the model is known as the pathogen-driven balancing selection or PDBS).…”

Section: Introductionmentioning

confidence: 99%

A New HLA Map of Europe: Regional Genetic Variation and Its Implication for Peopling History, Disease-Association Studies and Tissue Transplantation

Sanchez‐Mazas

Bühler

Nunes³

2013

Hum Hered

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Objectives: HLA genes are highly polymorphic in human populations as a result of diversifying selection related to their immune function. However, HLA geographic variation worldwide suggests that demographic factors also shaped their evolution. We here analyzed in detail HLA genetic variation in Europe in order to identify signatures of migration history and/or natural selection. Methods: Relationships between HLA diversity and geography were analyzed at 7 loci through several approaches including linear regression on gene diversity and haplotype frequencies. Regional variation was also assessed on HLA multi-locus phenotypes through structure analysis. Deviation from neutrality was tested by resampling. Results: Geographic distance was a strong predictor of HLA variation at 5 loci (A, B, C, DRB1 and DPB1) in Europe, and latitude significantly shaped HLA gene diversity and haplotype frequencies. Whereas the main level of genetic diversity was found within populations, both HLA gene frequencies and phenotypic profiles revealed regional variation, Southeast Europe, Great Britain and Finland being the most distinctive. Effects of natural selection were suggested at the DQ loci. Conclusions: HLA regional variation was observed in Europe and can be related to population history, locus HLA-A providing by far the strongest signals. This new HLA map of Europe represents an invaluable reference for disease-association studies and tissue transplantation.

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Common and well‐documented HLA alleles: 2012 update to the CWD catalogue

Cited by 207 publications

References 78 publications

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

Monoclonal antibodies to HLA‐E bind epitopes carried by unfolded β₂m‐free heavy chains

A New HLA Map of Europe: Regional Genetic Variation and Its Implication for Peopling History, Disease-Association Studies and Tissue Transplantation

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Common and well‐documented HLA alleles: 2012 update to the CWD catalogue

Cited by 207 publications

References 78 publications

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

Monoclonal antibodies to HLA‐E bind epitopes carried by unfolded β2m‐free heavy chains

A New HLA Map of Europe: Regional Genetic Variation and Its Implication for Peopling History, Disease-Association Studies and Tissue Transplantation

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Product

Resources

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Monoclonal antibodies to HLA‐E bind epitopes carried by unfolded β₂m‐free heavy chains