Major Histocompatibility Complex Genes

Abstract

Antigen binding by B cells occurs directly with the BCR recognizing epitopes on antigens. T cell recognition of antigens cannot occur unless the antigens are bound to major histocompatibility complex (MHC) proteins. A deficiency in MHC class I or II proteins results in failure of T cells to express CD4 or CD8 molecules in the thymus. The MHC genes encode proteins responsible for diversity of the immune response in individuals. The MHC genes are the most polymorphic in the human genome and include genes encoding glycoproteins responsible for recognition of alloantigens on foreign tissue such as transplantation antigens. MHC is a cluster of genes encoding class I, II and III proteins. Both class I and II MHC proteins are responsible for T cell restriction in its recognition of antigen. The gene clusters of class I and II are closely linked in all species. The genes are highly polymorphic, closely linked and therefore inherited together. The MHC genes contain many alternate forms referred to as alleles. The alleles are codominantly expressed and inherited as a set of alleles from each parent. Each set is known as a haplotype. There is no self/non-self-discrimination in the interaction with antigens. The selection pressures responsible for maintaining the close link are not well understood. The class III locus contains a cluster of unrelated genes encoding proteins that have importance in immunity but do not directly bind antigens. The MHC gene order on chromosomes varies from mouse to humans. All vertebrate species possess MHC or MHC-like collection of genes. MHC proteins are essential for both CD4⁺ and CD8⁺ T cell effector functions. Unlike B lymphocytes, which can recognize antigens directly, and can recognize epitopes that are conformationally constrained, T lymphocytes cannot recognize antigens directly and require that the antigens be processed to reveal internal hydrophobic peptides. These peptides bind to MHC molecules and the MHC-peptide complex becomes expressed on the surface of antigen presenting cells (APCs). In humans, MHC proteins are also known as human leukocyte antigens (HLA).