Steps of (a) introducing HLA gene into a fertilized egg or embryo of a non-human mammal, (b) transferring the fertilized egg or the embryo of the non-human mammal obtained in the step of (a) into a uterus of a female non-human mammal which is a foster mother, (c) breeding the female non-human mammal of a foster mother for a given period so that the mammal may reproduce transgenic non-human mammals, (d) administering anti-HLA antigen as immunogen into the transgenic non-human mammals which are obtained in the step of (c) and whose HLA genes introduced are expressed, (e) enucleating the spleen from the transgenic non-human mammals obtained in the step of (d) and making lymphocytes obtained from the spleen and myeloma cells to fuse, (f) selecting hybridomas which produce anti-HLA antibodies among the hybridomas obtained in the step of (e), and (g) culturing the selected hybridomas in vivo or in vitro to obtain anti-HLA monoclonal antibodies are comprised. In place of the above described steps of (a)-(c), steps of (a) transferring embryonal stem cells to which HLA genes are introduced into uterus of female non-human mammal of a foster mother simultaneously with an embryo of non-human mammal, (b) breeding the female non-human mammal of a foster mother so that the mammal may reproduce chimera individuals having HLA genes in their germ cells, and (c) performing a passage of the chimera individuals obtained in the step (b) to obtain transgenic non-human mammals having HLA genes in their all germ cells and somatic cells may also be conduced, and the steps on and after the above described step (d) may be similarly performed by utilizing this transgenic non-human mammal.
