CD1-Restricted T Cell Recognition of Microbial Lipoglycan Antigens

TLDR

T cells traditionally recognize peptide antigens via MHC, but nonpeptide lipoglycans can also be presented by CD1b, a non‑MHC molecule, expanding the range of microbial antigens recognized. Presentation of lipoglycans to T cells requires internalization and endosomal acidification. Human CD1b presents mycobacterial lipoarabinomannan to αβ TCR‑bearing lymphocytes, a recognition that depends on α(1→2) mannosides and a phosphatidylinositol unit, leading to IFN‑γ production and cytolysis, thereby demonstrating that lipoglycans are part of the foreign antigen repertoire.

Abstract

It has long been the paradigm that T cells recognize peptide antigens presented by major histocompatibility complex (MHC) molecules. However, nonpeptide antigens can be presented to T cells by human CD1b molecules, which are not encoded by the MHC. A major class of microbial antigens associated with pathogenicity are lipoglycans. It is shown here that human CD1b presents the defined mycobacterial lipoglycan lipoarabinomannan (LAM) to αβ T cell receptor-bearing lymphocytes. Presentation of these lipoglycan antigens required internalization and endosomal acidification. The T cell recognition required mannosides with α(1→2) linkages and a phosphatidylinositol unit. T cells activated by LAM produced interferon γ and were cytolytic. Thus, an important class of microbial molecules, the lipoglycans, is a part of the universe of foreign antigens recognized by human T cells.