The mycobacterial glycolipid glucose monomycolate induces a memory T cell response comparable to a model protein antigen and no B cell response upon experimental vaccination of cattle

Abstract

Glycolipids are presented to T cells by human group 1 CD1 proteins, but are not used as subunit vaccines yet. Experimental immunizations with pure mycobacterial glucose monomycolate (GMM) and keyhole limpet haemocyanin (KLH) in cattle, a species which, unlike mice, expresses group 1 CD1, showed that GMM was equally efficient as KLH in generating T cell responses in blood, but not in the draining lymph node. Also, KLH induced strong antibody responses whereas GMM did not. These data suggest that non-overlapping T cell populations are targeted and demonstrate the potential of glycolipids as a special class of subunit vaccine candidates.

Glucose monomycolates based on single synthetic mycolic acids

“…Cd1b tetramer staining of T cells has been used to prove that CD1b-glycolipid complexes bind the T cell receptor (Kasmar et al, 2011). GMM can induce a memory T cell response similar to a model protein antigen, and no B cell response; this has been applied in a new vaccination of cattle (Nguyen et al, 2009). Human T cells proliferate or produce interferon-in response to several types of mycobacterial lipid antigen presented by group 1CD1 proteins during latent or active tuberculosis infection, suggesting a function in host response to mycobacteria (Moody et al, 2000a,b;Ulrichs et al, 2003).…”

Targeted Delivery of Mycobacterial Antigens to Human Dendritic Cells via Siglec-7 Induces Robust T Cell Activation

“…Also, group 1 CD1-reactive T cells kill the Mycobacterium tuberculosis infected cells ex vivo (8, 9). Several studies show that group 1 CD1-restricted T cells expand and persist within individuals with tuberculosis (4, 5, 10), as well as animals vaccinated with the antigenic lipids (11, 12). These studies, along with the lack of common polymorphism of CD1 proteins in human populations, now provide the basis for considering lipid antigens as vaccines or immunodulatory agents that may provide protection from mycobacterial infections.…”

“…Accordingly T cells which recognize GMM from one source as their matched antigen also react to GMM from other sources (9). Further, animal studies suggest that GMM is an immunodominant antigen during natural infection (15, 16), and recent studies with CD1b tetramers prove that polyclonal populations of GMM-reactive T cells exist in human tuberculosis patients (4, 7). Of note, conserved ‘germline-encoded, mycolyl lipid-reactive’ (GEM) T cells have been identified as high-affinity responders to GMM in humans (7).…”

An Alternative Path for Antigen Presentation: Group 1 CD1 Proteins

“…However, the recent construction of a mouse transgenic for human CD1a, CD1b, and CD1c may make it possible to design an experiment in which protection can be demonstrated (23). Similarly few data on vaccination with lipid-linked Ags are available (24)(25)(26)(27). Of particular interest is a recent study of cattle immunized with mycobacterial glucose monomycolate (27).…”

“…Similarly few data on vaccination with lipid-linked Ags are available (24)(25)(26)(27). Of particular interest is a recent study of cattle immunized with mycobacterial glucose monomycolate (27). Cattle express CD1a, CD1b, and CD1c, but no CD1d.…”