CD1c restricts responses of mycobacteria-specific T cells. Evidence for antigen presentation by a second member of the human CD1 family.
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.
Beckman
E M
EM
Division of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Melián
A
A
Behar
S M
SM
Sieling
P A
PA
Chatterjee
D
D
Furlong
S T
ST
Matsumoto
R
R
Rosat
J P
JP
Modlin
R L
RL
Porcelli
S A
SA
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D018949:Antigens, CD1 / Q000145:classification / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008362:Mannosides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010716:Phosphatidylinositols / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000942:Antigens, Bacterial; D018949:Antigens, CD1; D008070:Lipopolysaccharides; D008362:Mannosides; D008562:Membrane Glycoproteins; D010716:Phosphatidylinositols; C050016:lipoarabinomannan