The effect of lipoylation on CD4 T-cell recognition of the 19,000 MW Mycobacterium tuberculosis antigen.

The mechanisms contributing to the dominant and degenerate recognition of the N-terminal region of the Mycobacterium tuberculosis 19,000 MW protein have been investigated. Using polyclonal and cloned T cells it was found that the apparently promiscuous response to the N-terminal peptide was due to the presence of multiple epitopes recognized in the context of different HLA determinants. This finding did not, however, explain the concentration of T-cell recognition on this part of the molecule. The 19,000 MW antigen is a lipoprotein, which raised the possibility that presence of a lipidation motif preceded by a signal peptide influenced the processing and presentation of the protein. Modified peptides covalently attached to lipid moieties were, therefore, tested on both polyclonal and cloned T cells. It was found that whilst lipoylation enhanced polyclonal T-cell recognition, the effect on cloned T cells was variable and depended on their epitope specificity and restricting HLA determinants. This suggested that whilst lipoylation may enhance some aspect of signalling for polyclonal T cells it does not affect the presentation of peptide to T-cell clones. The explanation for the immunodominance of the N-terminal region may, therefore, lie in some aspect of its processing.