title: Low cross-reactivity of T-cell responses against lipids from Mycobacterium bovis and M. avium paratuberculosis during natural infection.
abstract: Although CD1 proteins are known to present mycobacterial lipid antigens to T cells, there is little understanding of the in vivo behavior of T cells restricted by CD1a, CD1b and CD1c, and the relative immunogenicity and immunodominance of individual lipids within the total array of lipids that comprise a bacterium. Because bovines express multiple CD1 proteins and are natural hosts of Mycobacterium bovis and Mycobacterium avium paratuberculosis (MAP), we used them as a new animal model of CD1 function. Here, we report the surprisingly divergent responses against lipids produced by these two pathogens during infection. Despite considerable overlap in lipid content, only three out of 69 animals cross-react with M. bovis and MAP total lipid preparations. The unidentified immunodominant compound of M. bovis is a hydrophilic compound, whereas the immunodominant lipid of MAP is presented by CD1b and was identified as glucose monomycolate (GMM). The preferential recognition of GMM antigen by MAP-infected cattle may be explained by the higher expression of GMM by MAP than by M. bovis. The bacterial species-specific nature of the CD1-restricted, adaptive T-cell response affects the approach to development of lipid based immunodiagnostic tests.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
authors.forename: Thi Kim Anh
authors.initials: TK
authors.lastname: Nguyen
authors.forename: Anita
authors.initials: A
authors.lastname: Michel
authors.forename: Dave
authors.initials: D
authors.lastname: Cooper
authors.forename: Marc
authors.initials: M
authors.lastname: Govaerts
authors.forename: Tan-Yun
authors.initials: TY
authors.lastname: Cheng
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
authors.forename: Jacobus A W
authors.initials: JA
authors.lastname: Coetzer
authors.forename: Victor
authors.initials: V
authors.lastname: Rutten
authors.forename: Ad P
authors.initials: AP
authors.lastname: Koets
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D002417:Cattle; D003429:Cross Reactions; D008055:Lipids / Q000276:immunology*; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D010283:Paratuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D008055:Lipids
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