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RT1-U: Identification of a Novel, Active, Class Ib Alloantigen of the Rat MHC^{1 ,2}

Louise Y. W. Leong^*, Anne-France Le Rolle^*, Edward V. Deverson^*, Simon J. Powis, Audrey P. Larkins^*, John T. Vaage, Aasa Stokland, Doris Lambracht-Washington^§, Bent Rolstad, Etienne Joly^* and Geoffrey W. Butcher^3,*

^* Department of Immunology, The Babraham Institute, Cambridge, United Kingdom; Department of Biochemistry, University of Dundee, Dundee, United Kingdom; Department of Anatomy, University of Oslo, Blindern, Norway; and ^§ Transplantationslabor, Medizinische Hochschule, Hannover, Germany

In common with other mammalian species, the laboratory rat (Rattus norvegicus) expresses MHC class I molecules that have been categorized as either classical (class Ia) or nonclassical (class Ib). This distinction separates the class Ia molecules that play a conventional role in peptide Ag presentation to CD8 T cells from the others, whose function is unconventional or undefined. The class Ia molecules are encoded by the RT1-A region of the rat MHC, while the RT1-C/E/M region encodes up to 60 other class I genes or gene fragments, a number of which are known to be expressed (or to be expressible). Here we report upon novel MHC class Ib genes of the rat that we have expression cloned using new monoclonal alloantibodies and which we term RT1-U. The products detected by these Abs were readily identifiable by two-dimensional analysis of immunoprecipitates and were shown to be distinct from the class Ia products. Cellular studies of these molecules indicate that they function efficiently as targets for cytotoxic killing by appropriately raised polyclonal alloreactive CTL populations. The sequences of these class Ib genes group together in phylogenetic analysis, suggesting a unique locus or family. The combined serological, CTL, and sequence data all indicate that these products are genetically polymorphic.

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