CD1c restricts responses of mycobacteria-specific T cells. Evidence for antigen presentation by a second member of the human CD1 family

• Published in: The Journal of immunology (1950) Vol. 157; no. 7; pp. 2795 - 2803
• Main Authors: Beckman, EM, Melian, A, Behar, SM, Sieling, PA, Chatterjee, D, Furlong, ST, Matsumoto, R, Rosat, JP, Modlin, RL, Porcelli, SA
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.10.1996
• Subjects: Antigen Presentation; Antigens, Bacterial - immunology; Antigens, CD1 - classification; Antigens, CD1 - immunology; Cell Line; Humans; Lipopolysaccharides - immunology; Mannosides - immunology; Membrane Glycoproteins - immunology; Mycobacterium; Mycobacterium tuberculosis - immunology; Phosphatidylinositols - immunology; T-Lymphocyte Subsets - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.157.7.2795

Previous studies suggest that CD1 is a family of Ag-presenting molecules distantly related to those encoded by the MHC. However, of the four known human CD1 proteins, only CD1b has been shown to restrict Ag-specific T cell responses. In this study, we have shown that a second member of the human CD1 family, CD1c, could also mediate Ag presentation to T cells. Three T cell lines recognizing mycobacterial Ags in a CD1c-restricted manner were isolated from normal donor blood. These T cells were MHC unrestricted, and their recognition of Ag was independent of the products of the transporter associated with Ag presentation-1/2 and DMA/B genes that are generally required for Ag presentation by MHC-encoded Ag-presenting molecules. Furthermore, unlike MHC-restricted responses to peptides, the CD1c-restricted T cell lines recognized protease-resistant mycobacterial lipid Ags. These T cell lines also showed significant cytotoxicity toward CD1c-expressing target cells even in the absence of mycobacterial Ags, which was shown by clonal analysis to be mediated by a subpopulation of T cells directly reactive to CD1c molecules. Our findings establish the ability of a second member of the CD1 family to restrict responses of Ag-specific T cells, and thus support the general hypothesis that the CD1 family comprises a third lineage of Ag-presenting molecules that presents a novel class of foreign and self Ags to MHC-unrestricted T cells.