Mapping of the immune response genes in the major histocompatibility complex of the Rhesus monkey.

Abstract

Interest in the Ir genes of rheus monkeys stems from their phylogenetic relationship to man and the extensive data already available on the major histocompatibility complex of the monkey. At least two independent dominant H-linked Ir genes have been identified in the rhesus. These genes control the ability of monkeys to respond to the random linear copolymer of glutamyl alanine (GA), or the dinitrophenyl conjugate of glutamyl lysine (DNP-GL). These synthetic polymers can elicit weak delayed-type skin reactions and strong humoral responses in some monkeys. In a series of unrelated monkeys phenotyped for the serologically defined RhL-A specificities of both segregant series, there were no correlations between any RhL-A specificity and responder status to the GA or DNP-GL polymers. However, segregation analysis of 21 rhesus families sired by 3 fathers indicated the capacity of the offspring to form antibodies was associated with genes coded for in the RhL-A complex. In three monkeys, verified recombination within the RhL-A complex between the genes coding for the serologically defined determinants (SD loci) and the gene(s) controlling the lymphocyte-activating determinants (Lad loci) responsible for mixed lymphocyte reactivity was established. In two of these monkeys the immune response genes controlling the DNP-GL response segregated with the Lad genes, while in the third case the Ir-GL gene segregated with the SD loci, tentatively localizing the Ir-GL gene between the SD and Lad loci. In addition, we have shown that genetically distinct genes control responsiveness to DNP-GL and GA. These genes were separated by recombination, thus one monkey inherited the Lad, Ir-GL, and SD loci from one paternal haplotype and by crossing over inherited the gene controlling GA responsiveness from the other paternal haplotype. The fine structure mapping of the RhL-A gene complex is compared with the H-2 and HL-A gene complexes. Several striking similarities were noted.

A New Antigen System Expressed in Human Endothelial Cells

“…By analogy with homologous chromosomal regions in other species, the HLA region probably also controls cellular interactions and participates in the regulation of the immune response (10)(11)(12). The success of kidney allografts from HLA-matched siblings, in immunosuppressed hosts, is evidence that the HLA region is the main barrier to human kidney transplantation.…”

Multi-Locus control of MLC reactions in rhesus monkeys

“…The aberrant response with the HTC's can be explained in alternative ways, some of which are depicted in the lower part of Figure 1 (type 2). Since monkey GO had been found to be a recombinant for the RhLA-linked Ir-GL gene (Dorf et al 1975a), one possibility is that there is a second D locus 4 (D'), which maps in the vicinity of the Ir-GL gene. The two possible mapping positions of Ir-GL and D' are both depicted in Figure 1 (clearly D' and Ir-GL are mapped with respect to the crossover, not in relation to each other).…”

“…Antigens controlled by alleles at four RhLA marker loci, Ir-GL, Ial, B, and A are listed for each monkey, and the combinations of these alleles inherited en bloc (haplotypes) are indicated with the letters a, b (paternal), c, and d (maternal). Products of alleles at other RhLA marker loci are not included because the matings were uninformative with regard to alleles at the Bf (Ziegler et al 1975) and Ir-GA loci (Dorf et al 1975a Data are expressed as mean cpm _+ S.E. of triplicate cultures.…”

Immune Response Genes

“…Further work with inbred strains of mice, also employing synthetic polypeptide antigens, revealed the existence of several Ir genes in tbat species and made way for the startling discovery that the Ir genes were located within the major histocompatibility complex (MHC) -tbat in fact the Ir genes are histocompatibility genes (26), The same genomic location of Ir genes bas been demonstrated in the guinea pig (11), rat (16), and rhesus monkey (9), illustrating the generality of the phenomenon.…”