Structure and function of the CD1 family of MHC-like cell surface proteins

The CD1 family of proteins are structurally related to MHC class I proteins, but are only distantly related to the class I proteins or other MHC-linked class I-like proteins. Sequence comparisons indicate that the CD1 proteins have evolved into two subfamilies, those which are similar to human CD1a, b, and c and those which are similar to human CD1d. The CD1A-, B-, and C-like genes were deleted from rodents and the CD1D gene was duplicated. CD1a, b, and c are expressed by thymocytes, dendritic cells, activated monocytes, and B cells (CD1c), a tissue distribution which strongly suggests a role in antigen presentation. In contrast, CD1d and its murine homologues are expressed by many cells outside of the lymphoid and myeloid lineages. The CD1 proteins are in most cases expressed as beta 2mg-associated membrane glycoproteins, but may associate with additional proteins. CD1d is expressed on the surface of intestinal epithelial cells in a nonglycosylvated form without beta 2mg. Whether the CD1 proteins function as antigen-presenting molecules is unresolved, but it is unlikely that they present conventional peptide antigens. Strong evidence indicates that murine CD1 proteins are recognized by a population of NK1.1+, CD4+ or CD4-CD8- (double negative, DN) T cells which express an invariant TCR alpha chain. CD1d is most likely recognized by the homologous T cell population in humans. DN alpha beta T cells which recognize CD1a, b, or c have been isolated, including clones which recognize a lipid antigen from mycobacteria presented by CD1b. A third potential population of CD1 reactive cells are CD8+ T cells in the intestinal epithelium. Taken together, these observations indicate that CD1 proteins interact with several specialized populations of T cells. The precise biological functions mediated through these interactions remain to be determined.