TISSUE-SPECIFIC RECOGNITION OF MOUSE CD1 MOLECULES

Although there is evidence that some members of the CD1 gene family ma y present particular types of foreign Ags, such as mycobacterial lipid Ags or synthetic hydrophobic peptides, to alpha beta T cells, most CD 1 isotypes share the unusual property of being recognized by a high fr equency of naturally autoreactive alpha beta T cells. In the case of m ouse CD1.1 and its human counterpart CD1d, a significant fraction of t he autoreactive T cells express semi-invariant TCRs, CD1.1-specific T cells have a restricted tissue distribution and very promptly secrete a large panel of potent cytokines, including IL-4 and IFN-gamma, upon primary activation through their TCR, suggesting that they might regul ate some immune responses in these tissues. We show here that their au torecognition of mouse CD1.1 is highly dependent upon the cell type in which CD1.1 is expressed. For example, some of these T cells only res pond to CD1.1 expressed by splenic dendritic cells, some respond prefe rentially to cortical thymocytes, and others respond to splenic B cell s. Tissue specificity of CD1.1 recognition is also observed with vario us cell lines transfected with CD1.1 cDNA, These results show that dif ferent CD1.1 self Ags are expressed in different tissues and can be sp ecifically recognized by autoreactive T cells. They suggest that CD1.1 may be naturally associated with a variety of self ligands that overl ap only partially in different cell types.