The Journal of Immunology, Vol 139, Issue 6 1834-1839, Copyright © 1987 by American Association of Immunologists

ARTICLES

Comparison of antigen specificity, class II major histocompatibility complex restriction, and in vivo behavior of myelin basic protein- specific T cell lines and clones derived from (BALB/c x SJL/J) mice

J Trotter, SS Zamvil and L Steinman

Immunization with myelin basic protein (BP) causes experimental allergic encephalomyelitis (EAE) in certain strains of mice. SJL/J (H- 2s) is the prototype sensitive strain. Although BALB/c (H-2d) is resistant to EAE through use of an identical immunization protocol, (BALB/c x SJL/J)F1 hybrid mice develop EAE after immunization with BP. T cell clones specific for BP have been isolated from a highly encephalitogenic line of (BALB/c x SJL/J)F1 hybrid T cells raised against bovine BP. The clones were examined for their H-2 restriction and specificity for heterologous forms of BP (mouse, rat, and bovine BP). The results revealed the clones cross-reacting with mouse (self) BP were almost always restricted to F1 hybrid class II major histocompatibility complex (MHC) elements. In contrast, mouse cross- reactive clones derived from a nonencephalitogenic (BALB/c x SJL/J) T cell line raised against rat BP were largely restricted to H-2d elements. These clones did not cross-react with bovine BP. Four additional lines were generated by carrying the original rat and bovine F1 T cell lines on parental antigen-presenting cells thus generating lines biased toward homozygous (SJL/J, H-2s, or BALB/c, H-2d) restriction elements. These "parentally restricted" T cell lines did not induce EAE when injected in vivo. These results suggest that in this F1 strain sensitivity to T cell-induced EAE is associated with epitopes on murine BP that associate with F1 class II MHC restricting elements. In contrast, nonencephalitogenic T cell lines contain a high proportion of murine cross-reactive clones restricted to H-2d, the haplotype of the classically resistant BALB/c mouse. This work illustrates the use of T cell lines and clones in a model system to further analyze the role of MHC restriction elements in autoimmune disease occurring in heterozygous individuals.

This article has been cited by other articles:

				A. A. Hurwitz, T. J. Sullivan, R. A. Sobel, and J. P. Allison Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits the expansion of encephalitogenic T cells in experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice PNAS, February 20, 2002; (2002) 42684699. [Abstract] [Full Text] [PDF]

				C.-C. Chen, A. Rivera, N. Ron, J. P. Dougherty, and Y. Ron A gene therapy approach for treating T-cell-mediated autoimmune diseases Blood, February 15, 2001; 97(4): 886 - 894. [Abstract] [Full Text] [PDF]

				A. A. Hurwitz, T. J. Sullivan, R. A. Sobel, and J. P. Allison Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits the expansion of encephalitogenic T cells in experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice PNAS, March 5, 2002; 99(5): 3013 - 3017. [Abstract] [Full Text] [PDF]