Cross-reactive mycobacterial and self hsp60 epitope recognition in I-A(g7) expressing NOD, NOD-asp and Biozzi AB/H mice.
The highly conserved 60 kD endogenous heat shock protein (hsp60) has been suggested to be a target for T cell recognition in autoimmune diseases such as type I diabetes. We previously reported cross-recognition of both mycobacterial hsp60 (Mt60) and self hsp60 (m60) by Mt60 immunized NOD mice. To identify the epitopes involved, we generated T cell lines against m60 or its mycobacterial counterpart and tested these lines for recognition of complete sets of overlapping peptides spanning either hsp60 sequence. T cell lines responded to identical regions in the hsp60 proteins, regardless of their degree of conservation or I-A(g7) binding-affinity. Additionally, we determined whether a protective genetic background would affect the presence of hsp60 cross-reactive T cells in the peripheral repertoire by comparing epitope recognition in I-A(g7) expressing NOD, NOD-asp and Biozzi AB/H mice. Two out of five immunodominant murine peptides were able to induce proliferation in NOD and NOD-asp Mt60 T cell lines, but not in Biozzi AB/H T cell lines. Our results point out that Mt60 immunization not necessarily leads to proliferative T cells responding to endogenous hsp60 peptides in the context of diabetes-predisposing I-A(g7). Moreover, the capacity of T cells to respond to self hsp60 is not influenced by the presence of protective I-A(g7asp). Yet, proliferation of hsp60 autoreactive T cells is solely measured in combination with insulitis and as such serves as a surrogate marker for islet inflammation.
van Halteren
Astrid G S
AG
Department of Immunohematology and Blood Transfusion, Leids Universitair Medisch Centrum, The Netherlands. A.G.S.van_Halteren@lumc.nl
Roep
Bart O
BO
Gregori
Silvia
S
Cooke
Anne
A
van Eden
Willem
W
Kraal
Georg
G
Wauben
Marca H M
MH
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D018604:Epitope Mapping; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007114:Immunization; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D001324:Autoantigens; D018834:Chaperonin 60; D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen; D016056:Immunodominant Epitopes