**3. Adaptive immune responses**

#### **3.1. Allorecognition, T-cell activation, T cell–mediated cytotoxicity, and B lymphocytes**

The term allorecognition refers to recognition of diverse forms of genes between a member of the same species by T cells and involve Human major histocompatibility complex (MHC) glycoproteins. MHC is a family composed by the most studied antigens in transplantation field. These antigens are widely known as human leukocyte antigens (HLA). The genes encoding HLA antigens are highly polymorphic, this feature represents a big obstacle in the study of mechanisms of graft rejection. Class I HLA are present in membranes of the nucleated cell of humans and its function is to present small endogenous antigens to CD8 T lymphocytes. Class II are expressed on dendritic cells, macrophages, B cells, endothelial, and some types of epithelial cells. This T cell recognition event is the first step of graft rejection. There are two different ways in which T cells recognize alloantigens, i.e., direct and indirect. Direct recognition is when CD8+ and CD4+ T cells from the recipient recognize MHC class I and class II presented by APCs and donor peptides. Indirect recognition is mediated by specialized APCs form the recipient presenting to T cells [27]. Donor endothelial cells express molecules that stimulate T cells, these activated cells provide help to B cells resulting in the production of alloantibodies [28]. Although the most studied role of B cells is associated with alloantibodies and donor specific antibodies, there are controversial opinions about the deleterious role of these antibodies and its association with poor graft outcomes [29].
