Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells.
Major histocompatibility complex (MHC) class I and class II molecules bind immunogenic peptides and present them to lymphocytes bearing the alpha beta T-cell antigen receptor (TCR). An analogous antigen-presenting function also has been proposed for the non-MHC-encoded CD1 molecules, a family of non-polymorphic, beta 2-microglobulin-associated glycoproteins expressed on most professional antigen-presenting cells. In support of this hypothesis, CD1 molecules are recognized by selected CD4-CD8- alpha beta or gamma delta TCR+ T-cell clones, and we have recently shown that CD1 molecules restrict the recognition of foreign microbial antigens by alpha beta TCR+ T cells. But the substantial structural divergence of CD1 from MHC class I and class II molecules, raises the possibility that the antigens presented by the CD1 system may differ fundamentally from those presented by MHC-encoded molecules. Here we report that a purified CD1b-restricted antigen of Mycobacterium tuberculosis presented to alpha beta TCR+ T cells is mycolic acid, a family of alpha-branched, beta-hydroxy, long-chain fatty acids found in mycobacteria. This example of non-protein microbial antigen recognition suggests that alpha beta TCR+ T cells recognize a broader range of antigens than previously appreciated and that at least one member of the CD1 family has evolved the ability to present lipid antigens.
Beckman
E M
EM
Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, Massachusetts.
Porcelli
S A
SA
Morita
C T
CT
Behar
S M
SM
Furlong
S T
ST
Brenner
M B
MB
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D018949:Antigens, CD1; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009171:Mycolic Acids / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D015703:Antigens, CD; D018949:Antigens, CD1; D015395:Histocompatibility Antigens Class I; D009171:Mycolic Acids; D016693:Receptors, Antigen, T-Cell, alpha-beta