Differential rat T cell recognition of cathepsin D-released fragments of mycobacterial 65 kDa heat-shock protein after immunization with either the recombinant protein or whole mycobacteria |
| |
Authors: | van Noort Johannes M; Anderton Stephen M; Wagenaar Josee P A; Wauben Marca H M; van Holten Conny; Boog Claire J P |
| |
Institution: | Medical Biological Laboratory TNO PO Box 5815, 2280 HV, Rijswijk, The Netherlands
1 Institute of Immunology and Infectious Diseases PO Box 80165, 3508 TD, Utrecht, The Netherlands |
| |
Abstract: | T cells specific for the mycobacterial 65 kDa heat-shock protein(hsp65) play a pivotal role in the development of adjuvant arthritis(AA) in Lewis rats. Upon adoptive transfer, CD4+ T cells recognizinga particular hsp65 epitope trigger the onset of disease. Activationof hsp65-reactlve T cells can be achieved by immunization withheat-killed mycobacteria in mineral oil—complete Freund'sadjuvant (CFA)—or with purified recombinant hsp65. Arthritis,however, will only develop after immunization with CFA. In fact,prelmmunlzatlon with hsp65 protects against any subsequent attemptto induce AA. In this study, we examined polyclonal lymph nodecell responses in Lewis rats, Immunized with either CFA or purifiedrecombinant hsp65 in incomplete Freund's adjuvant, to a setof hsp65 fragments generated by a mild digestion with cathepsinD. Prollferatlve responses to several hsp65 fragments variedwith the type of antigen used for immunization. A cathepsinD-released fragment, Identified as residues 376–408, preferentiallytriggered proliferation of rat T cells after hsp65 Immunization.Prelmmunlzatlon of Lewis rats with this peptlde delayed theonset and reduced the severity of AA. Prelmmunlzatlon with anotherfragment which was preferentially recognized after CFA immunization,representing residues 40–60, did not have such a protectiveeffect. Our findings suggest the presence of mycobacterial hsp65determinants that selectively trigger AA-regulatlng T cellsand illustrate that cathepsin D may be used as an experimentaltool to generate such determinants. |
| |
Keywords: | adjuvant arthritis autoimmunity cathepsin D heat-shock protein T cell epitope |
本文献已被 Oxford 等数据库收录! |
|