Processing of Mycobacterium tuberculosis Bacilli by Human Monocytes for CD4 + αβ and γδ T Cells: Role of Particulate Antigen

Abstract

ABSTRACT Mycobacterium tuberculosis readily activates both CD4 + and Vδ2 + γδ T cells. Despite similarity in function, these T-cell subsets differ in the antigens they recognize and the manners in which these antigens are presented by M. tuberculosis -infected monocytes. We investigated mechanisms of antigen processing of M. tuberculosis antigens to human CD4 and γδ T cells by monocytes. Initial uptake of M. tuberculosis bacilli and subsequent processing were required for efficient presentation not only to CD4 T cells but also to Vδ2 + γδ T cells. For γδ T cells, recognition of M. tuberculosis -infected monocytes was dependent on Vδ2 + T-cell-receptor expression. Recognition of M. tuberculosis antigens by CD4 + T cells was restricted by the class II major histocompatibility complex molecule HLA-DR. Processing of M. tuberculosis bacilli for Vδ2 + γδ T cells was inhibitable by Brefeldin A, whereas processing of soluble mycobacterial antigens for γδ T cells was not sensitive to Brefeldin A. Processing of M. tuberculosis bacilli for CD4 + T cells was unaffected by Brefeldin A. Lysosomotropic agents such as chloroquine and ammonium chloride did not affect the processing of M. tuberculosis bacilli for CD4 + and γδ T cells. In contrast, both inhibitors blocked processing of soluble mycobacterial antigens for CD4 + T cells. Chloroquine and ammonium chloride insensitivity of processing of M. tuberculosis bacilli was not dependent on the viability of the bacteria, since processing of both formaldehyde-fixed dead bacteria and mycobacterial antigens covalently coupled to latex beads was chloroquine insensitive. Thus, the manner in which mycobacterial antigens were taken up by monocytes (particulate versus soluble) influenced the antigen processing pathway for CD4 + and γδ T cells.