Open MHC Class I Conformers: A Look through the Looking Glass

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Cell surface Major Histocompatibility Complex class I (MHC-I) molecules traditionally function in antigen presentation.
• Emerging evidence reveals MHC-I molecules possess significant non-immunological functions.
• These functions involve interactions with various cell surface receptors and signaling pathways.

Purpose of the Study:

• To review the diverse non-immunological functions of MHC-I molecules.
• To highlight the role of open MHC-I conformers in these functions.
• To discuss the implications of these findings in clinical and biomedical settings.

Main Methods:

• Literature review of studies on MHC-I functions.
• Analysis of research on cis-trans interactions of MHC-I with other receptors.
• Examination of the role of open MHC-I conformers.

Main Results:

• MHC-I molecules engage in cis-trans interactions with KIR, LILR, and receptors for hormones, growth factors, cytokines, and neurotransmitters.
• Open MHC-I conformers, heavy chains lacking β2m and peptide, are crucial for these non-immunological functions.
• These open conformers can associate with themselves, other receptors, and be shed extracellularly.

Conclusions:

• Open MHC-I conformers are multifunctional structures mediating non-immunological roles.
• These functions significantly impact autoimmune responses, tumor escape, transplantation, and neuronal development.
• Open MHC-I conformers fine-tune cell signaling, growth, differentiation, and intercellular communication.