AN ESTIMATE OF THE NUMBER OF HISTOCOMPATIBILITY LOCI IN THE RAT

The familiar reaction that leads to the rejection of tissue homografts has been studied in some detail in a fairly wide range of species and shown to be one of the most consistent and easily reproducible of all immunological responses.' Because the availability of several inbred strains has, until recently, been almost exclusively the prerogative of the mouse, this species has been the principal source of our quantitative knowledge of transplantation immunology, especially that concerned with its genetic aspects. It has been established that there are at least 14 different histocompatibility loci in this species, with multiple alleles at some of them; that the antigens determined by these various loci differ profoundly with respect to their relative strengths, those determined by a single locus, the H-2, exerting a predominating influence; and finally, that some of these loci appear to determine both red cell isoantigens and transplantation antigens.2'3 ro what extent the complexity of transplantation antigen determination in mice is indicative of the situation in other species is almost unknown at present. Because of their greater size, the facility with which they form easily detectable hemagglutinins in response to skin homografts,4a and the fact that isogenic or iso4b hav histogenic strains have been developed,5 rats may prove to be more advantageous than mice for studies on some of the current problems of transplantation immunology, including elucidation of the nature of the antigens responsible and their relationship to hemagglutinogens.3' 6 The purpose of this paper is to present the results of analyses conducted upon two inbred strains of rats of completely unrelated origin, designed (a) to confirm a previous suspicion that a Y-linked histocompatibility factor exists in this speciesO (Part 1) and (b) to obtain an estimate, on the basis of skin-grafting tests, of the number of histocompatibility loci at which these two strains differ (Part 2). Materials and Methods.-Rats: The two strains of rats used in this study originated in the Wistar Institute. The Lewis strain, of albino phenotype, now in its 37th generation of brother X sister mating, was initiated in 1945 by Margaret Lewis from animals taken from a closed, heterogeneous population of Wistar rats. The B. N. ("Brown Norway") strain, of chocolate phenotype, originated about 25 years ago from a mutant in Helen Dean King's colony of gray Norway rats, and was maintained as a very small pen-bred colony until 1958 by Paul Aptekmaii. At this time, it was found that skin grafts exchanged between randomly selected individuals from the colony were retained in impeccable condition for at least 100 days by about 30% of the hosts. Accordingly, starting with a brother/sister mating of rats compatible with each other's skin and using skin graft exchanges to select mutually compatible full-sibs from their offspring as parents for succeeding generations, a strain of rats was obtained within three generations that was almost completely uniform with respect to its histocompatibility genes. This was indicated by the acceptance, in cosmetically perfect condition for 100 days, of skin