**2. Human leukocyte antigen (HLA) system and allograft rejection**

Human leukocyte antigens (HLA) play a vital role in host defense against foreign pathogens and in immune surveillance of tumors. These antigens are encoded by the major histocompatibility complex (MHC) which is a family of genes that encompasses a 3.6 million base pair genomic region, 6p21, on the short arm of chromosome 6 [5]. The MHC complex is divided into three regions representing three classes of genes—classes I, II, and III. The HLA genes that are involved in the immune response belong to classes, I and II [6]. Class I antigens are expressed on all nucleated cells whereas class II antigens are expressed only on professional antigen presenting cells (APCs)—dendritic cells, B-cells, and macrophages [7]. In the setting of infection, pathogen derived foreign antigens are presented to T-cells as peptides on the surface of major histocompatibility complex (MHC) molecules expressed on the surface of APCs. The ensuing signaling cascade results in the activation, proliferation, and differentiation of naïve T lymphocytes into subtypes with distinct cytokine profiles. Type 1 helper T (Th1) cells drive the cellular immune response mediated by CD8+ cytotoxic T lymphocytes, and type 2 helper T (Th2) cells drive B-cell mediated humoral immune response [2].

The heterogeneity of human MHC molecules enables the immune system to protect us from a variety of foreign pathogens. However, in the context of transplantation between genetically distinct individuals, these MHC polymorphisms elicit immune responses that can result in rejection of the allograft [7]. Two pathophysiologically distinct flavors of renal allograft rejection are recognized—cell mediated, and antibody mediated rejection. Both these types of rejection can manifest as acute or chronic clinicopathologic variants. Acute cell mediated rejection is characterized by infiltration of the allograft by effector T cells resulting in the typical features such as tubulitis, interstitial inflammation and in more advanced cases, endothelial arteritis [2, 8].
