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Review
. 2019 Sep 13;20(18):4544.
doi: 10.3390/ijms20184544.

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

Tsukasa Nakamura  1 , Takayuki Shirouzu  2 , Katsuya Nakata  3 , Norio Yoshimura  4 , Hidetaka Ushigome  5
Affiliations
Review

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

Tsukasa Nakamura et al. Int J Mol Sci. .

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.

Keywords: donor specific anti-HLA antibodies; immunocomplex capture fluorescence analysis; major histocompatibility complex; organ transplantation.

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Conflict of interest statement

This study was funded by JSPS KAKENHI Grant Number 17K10518/19K18066, and Wakunaga Pharmaceutical Co., Ltd. Grant Number 29collaboration004. The funders had no role in the design of the study, interpretation of data, and the decision to publish the results.

Figures

Figure 1
Figure 1
The human leukocyte antigen (HLA-DR) region is divided into five groups, DR51, DR52, DR53, DR1, and DR8, depending on the number and combination of genes. Gray box indicates pseudogene.
Figure 2
Figure 2
A. Structure of HLA class I molecules. Endogenous antigens such as tumor cells and infected cells are presented as peptide. B. HLA class II structure. Exogenous antigens taken up by phagocytic cells are presented as peptide.
Figure 3
Figure 3
1.Direct pathway: CD4+ T cells activate and generate allograft-specific cytotoxic CD8+ T cells and humoral allo-immunity via donor antigen-presenting cells (APC). (Three-cell cluster). 2. Indirect pathway: recipient APC process donor antigens and present these molecules and activate CD4+ T cells, subsequently linked (Three-cell cluster) or non-linked CD8+ T cells (Four-cell cluster) can be activated by these CD4+ T cells help. 3. Semi-direct pathway: intact donor MHC class I molecules are reused by recipient APC.
See this image and copyright information in PMC

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