The Association of Immune Responsiveness, Mixed Lymphocyte Responses, and Ia Antigens in Natural Populations of Norway Rats

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Abstract
The major histocompatibility complex (MHC) of the rat has been separated into two regions. The A region contains genes that code for the classical histocompatibility (Ag-B/H-1) antigens, and the B region codes for the MLR, Ia antigens, and immune response to synthetic polypeptides. We have examined the relationship between MLR, Ia antigens, and the immune response to poly(Glu52Lys33Tyr15) in inbred rats and in a population of wild rats captured in a single location within the city of Pittsburgh. Antisera that define Ia antigenic specificities association with the RT1.Ba, RT1.Bl, and RT1.Bn MLR phenotypes in inbred rats detected the same MLR phenotype in each of 48 individual wild rats. This close association between Ia specificities and MLR phenotypes in a randomly breeding wild population suggests that the genes controlling the expression of these phenotypic strains are either tightly linked or that Ia antigens represent a stimulating determinant for the MLR. In the same population of wild rats, distinct high and low immune responses to the synthetic polypeptide poly(Glu52Lys33Tyr15) could be detected. Breeding studies demonstrated that the immune response to poly-(Glu52Lys33Tyr15) segregated with the MHC. There was a close association between high immune responsiveness and the RT1.Ba (Ia.4) MLR phenotype, and low responsiveness was usually associated with either the RT1.B1 (Ia.1) or RT1.Bn (Ia.3) MLR phenotypes. These same MLR and immune response associations are observed in inbred animals. The close association between alleles at different genetic loci in both the A and B regions of the rat MHC in natural populations is very similar to that reported for specific HLA haplotypes in man, suggesting that the rat may prove to be an important experimental model for studies involving the population dynamics of the genes in the MHC.