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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 August 2019) | Viewed by 24706

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Special Issue Editors

Prof. Dr. Jukka Partanen

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Guest Editor

Research and Development, Finnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, Finland
Interests: MHC; HLA; graft versus host disease; genetic variation
Special Issues, Collections and Topics in MDPI journals

Dr. Satu Koskela

E-Mail Website
Guest Editor

Research and Development, Finnish Red Cross Blood Service, Kivihaantie 7, FI-00310 Helsinki, Finland
Interests: MHC; classical HLA; non-clasical HLA; histocompatibility; KIR

Special Issue Information

Dear Colleagues,

The role of HLA genes and molecules, as well as the entire MHC gene region, is crucial in histocompatibility, infections and autoimmune diseases. While the knowledge on the immense variation in MHC inside and between populations has grown, the use of novel DNA- and cell molecular-technologies have become feasible and cost-effective. A Special Issue on the “Major Histocompatibility Complex” in the International Journal of Molecular Sciences is therefore much warranted and timely. The Special Issue on MHC is now open to receive manuscripts on all aspects of this highly variable gnomic region with particular emphasis on recent advances in the role of variation outside of the classical HLA class I and II polymorphism, both in disease susceptibility and histocompatibility. We are honored to have been invited to be guest editors for this issue and look forward to reading your contributions on MHC-related research.

Dr. Satu Koskela
Prof. Dr. Jukka Partanen
Guest Editors

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Keywords

MHC
HLA
histocompatibility
autoimmune disease
genetic variation
transplantation
SNP array
imputation
GWAS
NGS

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Published Papers (4 papers)

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Research

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11 pages, 1248 KiB

Open AccessArticle

HLA-F Allele-Specific Peptide Restriction Represents an Exceptional Proteomic Footprint

by Gia-Gia T. Hò, Funmilola J. Heinen, Rainer Blasczyk, Andreas Pich and Christina Bade-Doeding

Int. J. Mol. Sci. 2019, 20(22), 5572; https://doi.org/10.3390/ijms20225572 - 8 Nov 2019

Cited by 5 | Viewed by 2639

Abstract

Peptide-dependent engagement between human leucocyte antigens class I (HLA-I) molecules and their cognate receptors has been extensively analyzed. HLA-F belongs to the non-classical HLA-Ib molecules with marginal polymorphic nature and tissue restricted distribution. The three common allelic variants HLA-F*01:01/01:03/01:04 are distinguished by polymorphism outside the peptide binding pockets (residue 50, α1 or residue 251, α3) and are therefore not considered relevant for attention. However, peptide selection and presentation undergoes a most elaborated extraction from the whole available proteome. It is known that HLA-F confers a beneficial effect on disease outcome during HIV-1 infections. The interaction with the NK cell receptor initiates an antiviral downstream immune response and lead to delayed disease progression. During the time of HIV infection, HLA-F expression is upregulated, while its interaction with KIR3DS1 is diminished. The non-polymorphic nature of HLA-F facilitates the conclusion that understanding HLA-F peptide selection and presentation is essential to a comprehensive understanding of this dynamic immune response. Utilizing soluble HLA technology we recovered stable pHLA-F*01:01, 01:03 and 01:04 complexes from K562 cells and analyzed the peptides presented. Utilizing a sophisticated LC-MS-method, we analyzed the complete K562 proteome and matched the peptides presented by the respective HLA-F subtypes with detected proteins. All peptides featured a length of 8 to 24 amino acids and are not N-terminally anchored; the C-terminus is preferably anchored by Lys. To comprehend the alteration of the pHLA-F surface we structurally compared HLA-F variants bound to selected peptides. The peptides were selected from the same cellular content; however, no overlap between the proteomic source of F*01:01, 01:03 or 01:04 selected peptides could be observed. Recognizing the balance between HLA-F expression, HLA-F polymorphism and peptide selection will support to understand the role of HLA-F in viral pathogenesis. Full article

(This article belongs to the Special Issue Major Histocompatibility Complex (MHC))

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13 pages, 2099 KiB

Open AccessArticle

Differences in Expression of Human Leukocyte Antigen Class II Subtypes and T Cell Subsets in Behçet’s Disease with Arthritis

by S. M. Shamsul Islam, Hyoun-Ah Kim, Bunsoon Choi, Ju-Yang Jung, Sung-Min Lee, Chang-Hee Suh and Seonghyang Sohn

Int. J. Mol. Sci. 2019, 20(20), 5044; https://doi.org/10.3390/ijms20205044 - 11 Oct 2019

Cited by 5 | Viewed by 2350

Abstract

It has been reported Human Leukocyte Antigen (HLA) gene polymorphism is a risk factor for the development of Behçet’s disease (BD). In this study, the association of HLA class II subtypes HLA-DP, DQ, DR, and T cell subsets in BD patients with arthritis was evaluated. Frequencies of HLA-DP, DQ, DR positive cells, and T cell subsets in peripheral blood leukocytes (PBL) were measured by flow cytometric analysis in BD, and compared to rheumatoid arthritis as disease controls and healthy controls. Frequencies of HLA-DQ were significantly decreased in whole PBL and granulocytes of BD active patients as compared to healthy controls. In monocytes populations, proportions of HLA-DR positive cells were significantly increased in BD active patients as compared to healthy controls. Proportions of CD4+CCR7+ and CD8+CCR7+ cells were significantly higher in BD active patients than in BD inactive in whole PBL. Frequencies of CD4+CD62L- and CD8+CD62L- cells in lymphocytes were significantly decreased in active BD than those in inactive BD. There were also correlations between disease activity markers and T cell subsets. Our results revealed HLA-DP, DQ, and DR expressing cell frequencies and several T cell subsets were significantly correlated with BD arthritis symptoms. Full article

(This article belongs to the Special Issue Major Histocompatibility Complex (MHC))

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15 pages, 2037 KiB

Open AccessArticle

Human Leukocyte Antigen and Red Blood Cells Impact Umbilical Cord Blood CD34⁺ Cell Viability after Thawing

by Diana Vanegas, Cristian-Camilo Galindo, Iván-Aurelio Páez-Gutiérrez, Lorena-Xiomara González-Acero, Pavel-Tiberio Medina-Valderrama, Juan-Camilo Lozano, Bernardo Camacho-Rodríguez and Ana-María Perdomo-Arciniegas

Int. J. Mol. Sci. 2019, 20(19), 4875; https://doi.org/10.3390/ijms20194875 - 30 Sep 2019

Cited by 4 | Viewed by 5829

Abstract

Hematopoietic progenitor cell (HPC) transplantation is a treatment option for malignant and nonmalignant diseases. Umbilical cord blood (UCB) is an important HPC source, mainly for pediatric patients. It has been demonstrated that human leukocyte antigen (HLA) matching and cell dose are the most important features impacting clinical outcomes. However, UCB matching is performed using low resolution HLA typing and it has been demonstrated that the unnoticed mismatches negatively impact the transplant. Since we found differences in CD34⁺ viability after thawing of UCB units matched for two different patients (p = 0.05), we presumed a possible association between CD34⁺ cell viability and HLA. We performed a multivariate linear model (n = 67), comprising pre-cryopreservation variables and high resolution HLA genotypes separately. We found that pre-cryopreservation red blood cells (RBC), granulocytes, and viable CD34⁺ cell count significantly impacted CD34⁺ viability after thawing, along with HLA-B or -C (R² = 0.95, p = 0.01; R² = 0.56, p = 0.007, respectively). Although HLA-B*40:02 may have a negative impact on CD34⁺ cell viability, RBC depletion significantly improves it. Full article

(This article belongs to the Special Issue Major Histocompatibility Complex (MHC))

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Review

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22 pages, 1418 KiB

Open AccessReview

The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage -

by Tsukasa Nakamura, Takayuki Shirouzu, Katsuya Nakata, Norio Yoshimura and Hidetaka Ushigome

Int. J. Mol. Sci. 2019, 20(18), 4544; https://doi.org/10.3390/ijms20184544 - 13 Sep 2019

Cited by 24 | Viewed by 13403

Abstract

Organ transplantation has progressed with the comprehension of the major histocompatibility complex (MHC). It is true that the outcome of organ transplantation largely relies on how well rejection is managed. It is no exaggeration to say that to be well acquainted with MHC is a shortcut to control rejection. In human beings, MHC is generally recognized as human leukocyte antigens (HLA). Under the current circumstances, the number of alleles is still increasing, but the function is not completely understood. Their roles in organ transplantation are of vital importance, because mismatches of HLA alleles possibly evoke both cellular and antibody-mediated rejection. Even though the control of cellular rejection has improved by recent advances of immunosuppressants, there is no doubt that antibody-mediated rejection (AMR), which is strongly correlated with donor-specific anti-HLA antibodies (DSA), brings a poor outcome. Thus, to diagnose and treat AMR correctly is a clear proposition. In this review, we would like to focus on the detection of intra-graft DSA as a recent trend. Overall, here we will review the current knowledge regarding MHC, especially with intra-graft DSA, and future perspectives: HLA epitope matching; eplet risk stratification; predicted indirectly recognizable HLA epitopes etc. in the context of organ transplantation. Full article

(This article belongs to the Special Issue Major Histocompatibility Complex (MHC))

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