T-cell recognition of unconventional antigens

Abstract

CD1 proteins, expressed on many antigen presenting cells, are capable of binding lipids to form antigen complexes that contact T cell receptors and activate T cells. Invariant T cell populations exist in mycobacterium infected humans that recognize mycobacterial lipids. Other bacteria might also possess lipid antigens that activate T cells. Using an ELISPOT IFN- assay, we determined that lipids from pathogens other than mycobacteria can stimulate human IFN- responses. We generated T cell lines based on binding of CD1b loaded with lipid antigens. Analysis of T cell lines using ELISPOT revealed not only reactivity to CD1b loaded with S. aureus and B. melitensis lipid antigens, but also to untreated CD1b. A shared phospholipid between bacteria and mammalian cells, phosphatidyl glycerol, was determined to be the stimulating antigen. We sequenced the T cell receptor (TCR) from T cell lines using single cell PCR. Our data show that the identified TCR  and  chain genes are TRAV 9-2 in combination with TRBV 6-2. The identified TCR might play an important role in CD1 mediated immunity and potentially also in CD1 mediated autoimmunity, as phosphatidyl glycerol is also recognized as an antigen.