Major Histocompatibility Complex Class I Chain-Related A (MICA) Molecules: Relevance in Solid Organ Transplantation.

Ajay Kumar Baranwal,Narinder K Mehra

doi:10.3389/fimmu.2017.00182

Abstract

An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation. Humoral response to MICA antigens has repeatedly been associated with lower graft survival and an increased risk of acute and chronic rejection following kidney and liver transplantation with few studies showing conflicting results. Although there are clear indications of MICA antibodies being associated with adverse graft outcome, a definitive consensus on this relationship has not been arrived yet. Furthermore, only a few studies have dealt with the impact of MICA donor-specific antibodies as compared to those that are not donor specific on graft outcome. In addition to the membrane bound form, a soluble isoform of MICA (sMICA), which has the potential to engage the natural killer cell-activating receptor NKG2D resulting in endocytosis and degradation of receptor–ligand interaction complex leading to suppression of NKG2D-mediated host innate immunity, has been a subject of intense discussion. Most studies on sMICA have been directed toward understanding their influence on tumor growth, with limited literature focusing its role in transplant biology. Furthermore, a unique dimorphism (methionine to valine) at position 129 in the α2 domain categorizes MICA alleles into strong (MICA-129 met) and weak (MICA-129 val) binders of NKG2D receptor depending on whether they have methionine or valine at this position. Although the implications of MICA 129 dimorphism have been highlighted in hematopoietic stem cell transplantation, its role in solid organ transplantation is yet to be explored. This review summarizes the currently available information on MICA antibodies, soluble MICA, and MICA-129 dimorphism in a setting of solid organ transplantation.

Highlights

The Major Histocompatibility Complex (MHC) class I-related chain genes A and B (MICA and MICB) are a new family of proteins encoded within the human HLA class I genes, first described in 1994 by two independent groups of researchers [1, 2]
Only a few studies have dealt with the impact of MICA-donor-specific antibodies (DSA) as compared to those that are NDSA on graft outcome
Two factors are important while analyzing the role of MICA antibodies: (i) currently employed pretransplant crossmatch procedures are not sensitive enough to detect MICA DSA and (ii) the currently used immunosuppressants for induction and maintenance may not be effective in suppressing the immune response against MICA antigens because they are all directed at suppression of T cell response albeit through different mechanisms

Summary

Introduction

The Major Histocompatibility Complex (MHC) class I-related chain genes A and B (MICA and MICB) are a new family of proteins encoded within the human HLA class I genes, first described in 1994 by two independent groups of researchers [1, 2]. Following the first demonstration of the expression of MICA antigens on endothelial cells [10], attention was directed toward investigating the possibility of these molecules being a target for graft destruction in solid organ transplantation. In a study on 139 renal allograft recipients, Sumitran-Holgersson et al [40] showed a significant correlation of MICA antibodies with graft loss.

Results

Conclusion