Low cross-reactivity of T-cell responses against lipids from Mycobacterium bovis and M. avium paratuberculosis during natural infection.
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.
Van Rhijn
Ildiko
I
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands.
Nguyen
Thi Kim Anh
TK
Michel
Anita
A
Cooper
Dave
D
Govaerts
Marc
M
Cheng
Tan-Yun
TY
van Eden
Willem
W
Moody
D Branch
DB
Coetzer
Jacobus A W
JA
Rutten
Victor
V
Koets
Ad P
AP
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*
D000942:Antigens, Bacterial; D008055:Lipids
J Immunol. 2005 Mar 1;174(5):2637-44
15728470
J Exp Med. 2004 Mar 1;199(5):649-59
14981115
Infect Immun. 2001 Mar;69(3):1492-8
11179318
Science. 1995 Jul 14;269(5221):227-30
7542404
Nature. 2000 Apr 20;404(6780):884-8
10786796
Science. 1997 Oct 10;278(5336):283-6
9323206
Nature. 1994 Dec 15;372(6507):691-4
7527500
Clin Microbiol Rev. 2001 Jul;14(3):489-512
11432810
J Clin Microbiol. 1990 May;28(5):933-7
2351737
Int Immunol. 2003 Aug;15(8):915-25
12882829
J Exp Med. 2000 Oct 2;192(7):965-76
11015438
Science. 1997 Jun 13;276(5319):1684-7
9180075
Science. 2004 Jan 23;303(5657):527-31
14739458
Nat Immunol. 2002 May;3(5):435-42
11938350
Vaccine. 2006 Mar 24;24(14):2550-9
16417949
Trends Immunol. 2003 Aug;24(8):412-8
12909453
Vaccine. 2008 Jan 10;26(2):257-68
18068277
Acta Vet Scand. 1982;23(3):325-35
7180779
Vet Immunol Immunopathol. 2006 Nov 15;114(1-2):25-36
16904754
Tuberculosis (Edinb). 2006 Sep;86(5):363-73
16352469
J Biol Chem. 2008 Oct 24;283(43):28835-41
18703502
Tissue Antigens. 1999 Aug;54(2):122-7
10488738
Science. 1998 Oct 2;282(5386):121-5
9756476
Mol Immunol. 2009 Apr;46(7):1424-31
19185921
Microbes Infect. 2008 Jun;10(7):711-5
18538612
J Immunol. 1999 Nov 15;163(10):5478-88
10553074
Infect Immun. 2003 Jun;71(6):3076-87
12761085
J Immunol. 2006 Apr 15;176(8):4888-93
16585584