Mycobacterium lepraeand Leprosy: A Compendium

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.

Functional subsets of human T cells were delineated by analyzing patterns of lymphokines produced by clones from individuals with leprosy and by T cell clones of known function. CD4 clones from individuals with strong cell-mediated immunity produced predominantly interferon-gamma, whereas those clones that enhanced antibody formation produced interleukin-4. CD8 cytotoxic T cells secreted interferon-gamma. Interleukin-4 was produced by CD8 T suppressor clones from immunologically unresponsive individuals with leprosy and was found to be necessary for suppression in vitro. Both the classic reciprocal relation between antibody formation and cell-mediated immunity and resistance or susceptibility to certain infections may be explained by T cell subsets differing in patterns of lymphokine production.