HLA system in solid organ transplantation part 7

Biological role of MHC molecules

Broadly speaking, the role of class I MHC molecules in immune defence is to sample and present to T cells endogenous antigens present in the intracytoplasmic compartement. These antigens are typically derived from cells infected with intracellular microorganisms or from cancerous cells expressing mutated proteins, Thus, class I MHC molecules serve as a sensing mechanism of cellular health that, drastically and necessarily, lead to elimination of unhealthy cells by CD8 cytotoxic T cells. In transplantation, alloreactive cytotoxic T cells get activated by allogeneic donor cells expressing allogeneic class I MHC molecules. On the other hand, the defensive role of class II MHC molecules appears  to be the sampling  and presentation of exogenous antigen, reaching the lysosomal compartment, derived from extracellular microorganism. Since class II MHC molecules are expressed preferentially on antigen-presenting cell, their main role is to stimulate CD4 T cells to orchestrate different arms of the immune response. The restriction of class I MHC molecules to activate CD8 T cells and of class II MHC molecules activate CD 4 T cells is conferred at the molecular level by the presence of  a binding motif for CD8 in class I MHC molecules and for CD4 in class II MHC molecules, respectively. However exogenous antigens can also be presented by class I MHC molecules to activate CD8 cytotoxic T cells through the phenomenon of cross-presentation.