CD1c Restricts Responses of Mycobacteria-Specific T Cells: Evidence for Antigen Presentation by a Second Member of the Human CD1 Family

Evan M. Beckman, Agustín Melián, Samuel M. Behar, Peter A. Sieling, Delphi Chatterjee, Stephen T. Furlong, Ryoji Matsumoto, Jean Pierre Rosat, Robert L. Modlin, Steven A. Porcelli

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Abstract

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 CDTc-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.

Original languageEnglish (US)
Pages (from-to)2795-2803
Number of pages9
JournalJournal of Immunology
Volume157
Issue number7
StatePublished - Oct 1 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Beckman, E. M., Melián, A., Behar, S. M., Sieling, P. A., Chatterjee, D., Furlong, S. T., Matsumoto, R., Rosat, J. P., Modlin, R. L., & Porcelli, S. A. (1996). CD1c Restricts Responses of Mycobacteria-Specific T Cells: Evidence for Antigen Presentation by a Second Member of the Human CD1 Family. Journal of Immunology, 157(7), 2795-2803.