SelfMHC

SelfMHC refers to the Major Histocompatibility Complex molecules expressed by an individual’s own cells and the self-derived peptide fragments they present on the cell surface. In humans, these molecules are encoded by the HLA gene region. MHC molecules come in two main classes: class I proteins, which are present on almost all nucleated cells and present endogenous peptides to CD8+ cytotoxic T cells; and class II proteins, found mainly on professional antigen-presenting cells, which present exogenous peptides to CD4+ helper T cells. Together, selfMHC–peptide complexes enable immune surveillance and self–non-self discrimination.

A central feature of selfMHC biology is T cell education. T cells undergo positive selection in the thymus to ensure they can recognize selfMHC molecules, and negative selection to eliminate cells that bind selfMHC too strongly with self-peptides. This establishes central tolerance to self antigens. Peripheral tolerance mechanisms, including regulatory T cells and anergy, provide additional control to prevent autoimmunity when encountering selfMHC in the periphery.

The concept of selfMHC underpins MHC restriction, the idea that T cell receptors specifically recognize a peptide in the context of the host’s own MHC alleles. In clinical and research contexts, selfMHC is contrasted with foreign or allogeneic MHC, where mismatches can provoke immune responses such as graft rejection or graft-versus-host disease.

Human MHC genes are highly polymorphic, so individuals express a limited set of MHC alleles that influence peptide presentation and immune responsiveness.