Major Histocompatibility Complex - MHC in Animal Immunity

MHC in Animal Immunity

Of the three MHC classes identified, human focus commonly goes to class I and class II. MHC class II mediates immunization—specific immunity—to an antigen. MHC class I thereafter mediates destruction of host cells displaying that antigen.

Some mature leukocytes of the lineage lymphocyte—residing in peripheral lymphoid tissues such as lymphoid follicles and lymph nodes—bear receptors that ligate MHC. T cells, which are lymphocytes of specific immunity, as well as natural killer cells (NK cells), which are lymphocytes that act innately, interact with MHC. When MHC class I expression is low altogether—suggesting abnormal cell function—NK cells prompt programmed cell death of the cell. (B cells, the other lymphocyte mediating specific immunity, secrete antibody molecules, but do not ligate MHC.)

MHC class II can be conditionally expressed by all cell types, but normally occurs only on professional antigen-presenting cells (APCs): macrophages, B cells, and especially dendritic cells (DCs). An APC uptakes an antigen, performs antigen processing, and returns a molecular fraction—the epitope—to the APC's surface within an MHC class II molecule for antigen presentation. The CD4 receptors borne by naive helper T cells ligate MHC class II while the epitope—within the MHC class II molecule—imprints the T cell receptor (TCR) of the naive helper T cell, memorizing that epitope. The APC meanwhile secretes cytokines prompting differentiation of the helper T cell (Th) from naive phenotype (Th0) into a particular effector phenotype, either type 1 (Th1), type 2 (Th2), type 17 (Th17), or regulatory phenotype (Treg), as so far identified. Thus MHC class II mediates immunization to—or, if helping prime Treg, mediates immune tolerance of—an antigen.

MHC class I occurs on all nucleated cells—in essence all cells but red blood cells. MHC class I presents epitopes to cytotoxic T cells, also called killer T cells, which express the CD8 molecule. When its CD8 docks to MHC class I, if its TCR recognizes its matching epitope, the killer T cell induces the cell's apoptosis. Thus MHC class I helps mediate cellular immunity. (B cells express MHC class II to present antigen to Th0, but when its B cell receptor is ligated by its own matching epitope—an interaction not mediated by MHC—the activated B cell secretes soluble immunoglobulins: antibody molecules mediating humoral immunity.)