Histocompatibility Studies in a Closely Bred Colony of Dogs

Abstract

The segregation of the canine DL-A leukocyte group antigen(s) b, c, d, e, f, g, h, k, l, and m has been traced in 141 consecutive matings in the Cooperstown Colony of beagles. All of the leukocyte antigen(s) were regularly transmitted en bloc from parent to offspring, with no instance of independent segregation. A total of 23 haplotypes, including six different DL-A antigen patterns (gl, bkhfm, bkcd, e, be, fgl) was observed. 31 different DL-A phenotypes were observed in a population of 100 mongrel dogs. A number of statistically significant positive and negative associations between individual DL-A antigenic components occurred in this population. The results support the concept of the DL-A system as a complex immunogenetic system governed by a single region (or locus) of an autosomal pair of chromosomes. Studies of skin, kidney, heart, and liver allografts in the Cooperstown Colony indicated that the longest allograft survivals occur under genetically and serologically defined conditions of donor-recipient DL-A compatibility. Skin and renal allografts generally behaved in parallel fashion, while cardiac allografts survived for longer periods of time (MST = 47.1 days) than kidneys (MST = 28.1 days) or skin (MST = 25.1 days) under conditions of DL-A identity. Heart transplants were rejected at a more rapid rate than kidney, however, in DL-A-incompatible donor-recipient combinations. Liver transplants were accorded the longest survival time (MST = 76.2 days) under conditions of DL-A identity, but were rejected at a rapid rate (MST = 5 days) in DL-A-incompatible nonlittermate donor-recipient pairs. The results provide further evidence that the DL-A system is the principal system of histocompatibility in the canine species. The differences in survival of different organs under similar conditions of donor-recipient DL-A compatibility suggest, however, the existence of a number of unknown variables which may also be capable of significantly affecting allograft behavior.

Induction of Allogeneic Unresponsiveness in Adult Dogs

“…In contrast, skiin grafts fromii a thirdl (lonior bearing pedigree-ideintical DLA haplotypes were rejectedl by eight of nine recipienits within 13.5-41 daxys; one graft survived for 84 dlays and one for 132 (lays. (3,4,10). The studies of Storb and associates (20,21) and of Vriesendorp et al (22) have provided additional evidence for the activity of such non-DLA histocompatibility complex(es) in canine transplantation.…”

“…The superabundance of apparent antigenis on some haplotypes (e.g., 0, which appears to transmit no less than five SD antigenis) may be due to cross-reactivity or to the lack of ability to distiiiguish between public specificities which are comimiiloIn to several alleles and private specificities which have a very restricted distribution (10). Similarly, the dletectioii of only oiie product of the "l " haplotvpe may be a conse(quience of the lack of c.ompleteness of the repertoire of available anltisera.…”

“…The assignmiient of haplotypes to individual members of the Cooperstown colony was made possible through family studies (10 Allogen1eic U_Trespon5iveness in Adult Dogsthe 23 recognized haplotypes. These 23 identifiable haplotypes fall into the six patterns represented symbolically as m, *, -, V, I, and A, so that in certain instances, many haplotypes may have been assigned to the same phenotype on the basis of serology.…”

Histocompatibility Studies in a Closely Bred Colony of Dogs

“…This result, taken together with evidence that such leukocyte antigens behave as Mendelian autosomal dominants in the Cooperstown Colony (41), suggested that these leukocyte antigens were components of a single major system of histocompatibility, for which the term DL-A was proposed (37). different DL-A haplotypes (i.e., specificities, or sets of specifieifies, determined by the DL-A region of one chromosome) in this colony (46), and have demonstrated that all currently known DL-A antigen(s) are regularly transmitted en bloc from parents to offspring, with no evidence of independent segregation. These studies have also resulted in the definition of the DL-A genotypes of 1302 offspring of 517 matings in the Cooperstown Colony (46).…”

“…different DL-A haplotypes (i.e., specificities, or sets of specifieifies, determined by the DL-A region of one chromosome) in this colony (46), and have demonstrated that all currently known DL-A antigen(s) are regularly transmitted en bloc from parents to offspring, with no evidence of independent segregation. These studies have also resulted in the definition of the DL-A genotypes of 1302 offspring of 517 matings in the Cooperstown Colony (46). Preliminary studies (47,48) have raised the possibility that the application of such genotypic criteria of donor-recipient DL-A identity might considerably improve the results of bone marrow transplantation in the canine species (49).…”