**1. Introduction**

In this chapter, we will explore the effect of human leukocyte antigen (HLA) matching on renal transplant outcomes. The importance of HLA matching has been clearly established in renal transplantation and the extent of HLA mismatches at the A, B and DR loci form an important part in the assessment of the immunological risk of potential transplant candidates. Increasing number of HLA mismatches has been shown to be associated with poorer graft and patient survival following kidney transplantation but the ongoing importance of this association in the era of more potent immunosuppression and improved donor selection remains unclear. Nevertheless, HLA mismatches remain a crucial component of deceased donor kidney allocation in most countries including the United States and Australia. As a result of major advances in technology, HLA-typing has evolved from serological-based typing to molecular HLA-typing and solid-phase anti-HLA-antibody-detection assays, which have had a major influence in both allocation and outcome of transplanted kidneys. The identification of donorspecific anti-HLA-antibody (DSA) has become standard practice and cross-matching assays to establish the presence of DSA has evolved from complement-dependent cytotoxicity (CDC) assay to the exquisitely sensitive flow-cytometric and solid-phase assays. The availability of these sensitive assays has enable clinicians to perform calculated panel reactive antibody and virtual cross-match, which has led to a more accurate assessment of immunological risk of potential transplant candidates and improvement in the allocation of deceased donor kidneys. Defining the appropriate threshold values for clinically relevant DSA assignment, the ongoing significance of HLA-matching in the presence of DSA and the importance of anti-HLA-Cw, HLA-DQ and HLA-DP antibodies remain poorly defined. Finally, we will discuss the process of identifying acceptable HLA-mismatches using HLAMatchmaker, which determines HLA-

© 2013 Nguyen et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

compatibility at the level of polymorphic amino acid triplets or eplets in antibody-accessible regions, and the benefit of acceptable HLA-mismatch programs in improving the transplant potential of highly sensitized transplant candidates.

**2.1. Dendritic cells (Figure 2)**

T-helper cells. These CD4+

macrophages, NK cells, and eosinophils) effector cells.

Dendritic cells (DC) are a group of rare, heterogenous population of professional antigenpresenting cells (APC) that can initiate primary immune responses, and hence have the ability to regulate both innate and adaptive immune responses [2-4]. Precursor DC (pre-DC), arising from bone marrow progenitors, enter tissues as immature DC with superior phagocytic capabilities. DC encounter foreign antigens such as donor antigens (in solid organ transplan‐ tation), bacteria and tumour antigens resulting in the secretion of cytokines (e.g. IFN) and activation of natural killer (NK) cells, macrophages and eosinophils. Following antigen capture and processing, DC undergo maturation and migrate to secondary lymphoid tissues where they present processed antigen/peptide coupled to major histocompatibility complexes (MHC) to T cells, allowing for selection and expansion of antigen-specific cluster designation (CD)4+

regulating antigen-specific (e.g. CD8+ cytotoxic T cells, B cells), and antigen non-specific (e.g.

**Overview of the complex relationship between dendritic cells and effector T and B cells.** Immature DC (MDC and PDC) maturate in response to appropriate stimuli (e.g. microbial products, TLR ligands). Mature DC secretes immunor‐ egulatory cytokines (including IFN-α and IL-12] and with cell-cell contact, modulates effector cell response including NK cells, B and T cells as well as providing a positive feedback to DC to initiate ongoing activation and maturation. Activated effector cells could in turn modulate DC activation, maturation, and survival as well as enhancing other ef‐

DC play a critical role in the initiation and regulation of adaptive T cell responses, the main‐ tenance of central and peripheral tolerance in normal steady-state and hence are essential in

fector cell functions through the production of cytokines (IFN-γ) and/or via cell-cell contact.

**Figure 2.** Interaction between dendritic cells and effector T and B cells.

**Stimulus (e.g. donor-derived MHC peptides)**

T-helper cells subsequently amplify the immune responses by

The Evolution of HLA-Matching in Kidney Transplantation

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