Homotypic and heterotypic in cis associations of MHC class I molecules at the cell surface

Through the presentation of peptide antigens to cytotoxic T lymphocytes, major histocompatibility complex (MHC) class I molecules mediate the adaptive immune response against tumors and viruses. Additional non-immunological functions include the heterotypic association of class I molecules with cell surface receptors, regulating their activities by unknown mechanisms. Also, homotypic associations resulting in class I dimers and oligomers - of unknown function - have been related to pathological outcomes. In this review, we provide an overview of the current knowledge about the occurrence, biochemical nature, and dynamics of homotypic and heterotypic associations of class I molecules at the cell surface with special focus on the molecular species that take part in the complexes and on the evidence that supports novel biological roles for class I molecules. We show that both heterotypic and homotypic class I associations reported in the literature describe not one but several kinds of oligomers with distinctive stoichiometry and biochemical properties. [Display omitted] •Major histocompatibility complex class I molecules form homotypic and heterotypic associations at the cell surface.•Associations show distinctive stoichiometry and biochemical properties.•Associations might regulate immunological and non-immunological processes.•Heterotypic association with cell surface receptors might regulate receptor's activity.•Homotypic associations have been related to pathological outcomes.