Mixed-Haplotype and Mixed-Isotype Major Histocompatibility Complex Class II Molecules Detected by Murine T-Cell Clones and Their Possible Involvement in Autoimmunity.

The recognition of antigen by T lymphocytes (T cells) is restricted by Class I or Class II major histocompatibility complex (MHC) gene products, the phenomenon called "MHC restriction." MHC restriction is speculated to be one of the major elements for the association of disease susceptibility to MHC haplotypes. Clones of T cells have been shown to be powerful tools for the analysis of such restriction specificity. In this report, I describe unique mixed-isotype Abetad/Ealphad restriction molecules detected by T-cell clones in (B6Ealphad x BALB/c)F1 transgenic mice. The restriction specificity of these clones was confirmed by anti-Class II mAb blocking experiments. The ability of spleen cells from Abetad and Ealphad double transgenic B6 (B6AbetadEalphad) mice that express Abetad/Ealphad molecules to present KLH to these clones supported the existence of such unique specificity. I also describe autoreactive as well as KLH-reactive T-cell clones restricted by mixed-haplotype Abetaz/Aalphad Class II molecules derived from (NZB x NZW)F1 (B/WF1) mice. The restriction specificity was demonstrated by mAb blocking experiments and by experiments using Class II gene-transfected antigen-presenting cells. It is possible that such unique mixed-isotype and mixed-haplotype Class II molecules are critically involved in autoimmunity. In addition, the detailed methodology for establishing T-cell clones currently employed in my laboratory is described.