ABSTRACT
The major histocompatibility complex (MHC) locus located on the short arm of human chromosome six contains a family of highly polymorphic genes whose predominant role is to present both foreign and self-antigens to the immune system. Within the MHC locus are a set of genes encoding the surface-expressed HLA (human leukocyte antigens) molecules responsible for presenting antigen to T cells. These are divided into Class I molecules (A, B, and C) that present antigen to CD8 T cells and Class II molecules (DR, DQ, and DP) that present antigen to CD4 T cells. In peripheral immunity, T cells recognize foreign proteins as peptides bound to surface-expressed HLA molecules on antigen-presenting cells (APC). Activated T cells then act in a concerted effort with other immune cells to eliminate the source of these non-self antigens. In the context of organ transplantation, incompatibility between donor and recipient is dependent on T cell recognition of differences in the polymorphic MHC regions and is a major factor determining whether the donor organ will be accepted or rejected within a host. In autoimmune disease, self-antigens presented on HLA molecules are a driving force in directing a T cell immune response. A sustained state of this autoreactivity against selfantigens leads to tissue damage; thus, in insulin-dependent diabetes mellitus (IDDM), autoreactivity leads to the destruction of insulin-secreting pancreatic beta cells, autoreactivity in rheumatoid arthritis (RA) results in a loss of joint synovium, and various autoimmune syndromes are associated with multiple tissue damage including skin, nervous system, and kidney.
