Qa-1, a nonclassical class I histocompatibility molecule with roles in innate and adaptive immunity

• Published in: Immunologic research Vol. 29; no. 1-3; pp. 81 - 92
• Main Authors: Jensen, Peter E, Sullivan, Barbara A, Reed-Loisel, Lisa M, Weber, Dominique A
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.01.2004
• Subjects: Animals; Antigens, CD - immunology; Cellular biology; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - physiology; HLA Antigens - immunology; HLA-E Antigens; Immune system; Immunity, Active; Immunity, Innate; Immunology; Insulin - immunology; Killer Cells, Natural - immunology; Lectins, C-Type - immunology; Mice; Molecular biology; NK Cell Lectin-Like Receptor Subfamily C; NK Cell Lectin-Like Receptor Subfamily D; Peptides; Receptors, Immunologic - immunology; Receptors, Natural Killer Cell; T cell receptors; T-Lymphocytes - immunology
• ISSN: 0257-277X; 0257-277X; 1559-0755
• DOI: 10.1385/ir:29:1-3:081

Qa-1, a nonclassical class I histocompatibility molecule expressed in mice, predominantly assembles with a single nonameric peptide, Qdm, derived from the signal sequence of certain class Ia molecules. The Qa-1/Qdm complex is the primary ligand for CD94/NKG2A inhibitory receptors expressed on a major fraction of natural killer (NK) cells. Cells become susceptible to killing by NK cells under conditions where surface expression of the Qa-1/Qdm inhibitory ligand is reduced. The CD94/NKG2 "missing-self" recognition system serves as mechanism for removing cells that have abnormalities in the intracellular machinery required for assembly and expression of class I-peptides complexes, as a consequence of viral infection, for example. Despite its highly focused peptide-binding specificity, Qa-1 also has a capacity to act as an antigen-presentation molecule for CD8+ T cells. It appears that a small subpopulation of these T cells undergoes positive selection by interaction with Qa-1 in the thymus, and they maintain their specificity for Qa-1 after maturation. The role of these unusual T cells in adaptive immune responses remains to be defined.