High-resolution mapping of a minor histocompatibility antigen gene on mouse chromosome 2.

Minor histocompatibility (H) loci are significant tissue transplantation barriers but are poorly understood at the genetic and molecular level. We describe the construction of a high-resolution genetic map that positions a class II MHC-restricted minor H antigen locus and orders 12 other genes and genetic markers within the we-un interval of mouse Chromosome (Chr) 2. An intersubspecific backcross between B10.UW/Sn-H-3b and CAST/Ei, an inbred stock of Mus musculus castaneus, was used for this purpose. A total of 1168 backcross mice were generated, and 71 we-un recombinants were identified. Significant compression of the genetic map in males versus females and transmission distortion of CAST-derived we, un, and Aw genes were observed. Monoclonal T cell lines specific for two minor H alloantigens, Hd-1a and Hd-2a, encoded by gene(s) that map to the we-un interval were used to antigen type the backcross mice. The results suggest the Hd-1a and Hd-2a antigens are most likely encoded by a single gene, now referred to as H-3b. The determined gene order is we-0.09 +/- 0.09-Itp-0.62 +/- 0.23-D2Mit77-0.26 +/- 0.15-[Evi-4, Pcna, Prn-p]-0.26 +/- 0.15-Scg-1-0.44 +/- 0.19-[Bmp2a, D2Mit70]-0.09 +/-. 0.09-[D2Mit19, D2Mit46]-1.59 +/- 0.36-D2Mit28-0.97 +/- 0.28-D2Ler1-1.50 +/- 0.35-H-3b-0.26 +/- 0.15-un (% recombination +/- 1 SE). Because the average resolution of the backcross is 0.09 cM, the backcross panel should facilitate the physical mapping and molecular identification of a number of genes in this chromosome region